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Vignesh, R., Ganesh, P. S., Sankar, S., Chattopadhyay, I., Yong, Y. K., Larsson, M. & Shankar, E. M. (2023). Gut Microbiota Peculiarities in Aged HIV-Infected Individuals: Molecular Understanding and Therapeutic Perspectives. In: Marotta, Francesco (Ed.), Gut Microbiota in Aging and Chronic Diseases: (pp. 415-439). Cham: Springer
Open this publication in new window or tab >>Gut Microbiota Peculiarities in Aged HIV-Infected Individuals: Molecular Understanding and Therapeutic Perspectives
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2023 (English)In: Gut Microbiota in Aging and Chronic Diseases / [ed] Marotta, Francesco, Cham: Springer , 2023, p. 415-439Chapter in book (Refereed)
Abstract [en]

Aging is a progressive physiological process that involves alterations in the population of normal gutGut microbiotaGut microbiota. HIV infectionHIV infection in conjunction with agingAgeing complicates the quality of immune responses paving way for increased epithelial permeability and translocation of commensals and pathogen-derived substances into the systemic circulation. Enteric dysbiosisDysbiosis is linked with other comorbidities of agingAging including cardiovascular diseases and dementia in the HIV-infected population. The diversity of gutGut microbiotaGut microbiota declines with ageAge, and HIV infectionHIV infection compromises the effective functioning of the immune system complicating the metabolic as well as regulatory programming of the host’s physiological machinery. Given the scenario of the global HIV/AIDS and the COVID-19 pandemics, it is also likely that alterations in gutGut microbiotaGut microbiota potentially could contribute to post-acute COVID-19 syndrome as well as accelerate the rate of HIV disease progression. The current chapter discusses the role of normal gutGut microbiotaGut microbiota in the aged HIV-infected population and their functional implications in normal cellular and molecular mechanisms in the host.

Place, publisher, year, edition, pages
Cham: Springer, 2023
Series
Healthy Ageing and Longevity, ISSN 2199-9007, E-ISSN 2199-9015 ; 17
Keywords
Aging; Dysbiosis; HIV infection; Microbiota; SARS-CoV-2
National Category
Infectious Medicine
Identifiers
urn:nbn:se:liu:diva-197180 (URN)10.1007/978-3-031-14023-5_20 (DOI)9783031140228 (ISBN)9783031140235 (ISBN)
Available from: 2023-08-24 Created: 2023-08-24 Last updated: 2023-11-02Bibliographically approved
Hopkins, F. R., Govender, M., Svanberg, C., Nordgren, J., Waller, H., Nilsdotter-Augustinsson, Å., . . . Larsson, M. (2023). Major alterations to monocyte and dendritic cell subsets lasting more than 6 months after hospitalization for COVID-19. Frontiers in Immunology, 13, Article ID 1082912.
Open this publication in new window or tab >>Major alterations to monocyte and dendritic cell subsets lasting more than 6 months after hospitalization for COVID-19
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2023 (English)In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 13, article id 1082912Article in journal (Refereed) Published
Abstract [en]

Introduction: After more than two years the Coronavirus disease-19 (COVID-19) pandemic continues to burden healthcare systems and economies worldwide, and it is evident that the effects on the immune system can persist for months post-infection. The activity of myeloid cells such as monocytes and dendritic cells (DC) is essential for correct mobilization of the innate and adaptive responses to a pathogen. Impaired levels and responses of monocytes and DC to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is likely to be a driving force behind the immune dysregulation that characterizes severe COVID-19.

Methods: Here, we followed a cohort of COVID-19 patients hospitalized during the early waves of the pandemic for 6-7 months. The levels and phenotypes of circulating monocyte and DC subsets were assessed to determine both the early and long-term effects of the SARS-CoV-2 infection.

Results: We found increased monocyte levels that persisted for 6-7 months, mostly attributed to elevated levels of classical monocytes. Myeloid derived suppressor cells were also elevated over this period. While most DC subsets recovered from an initial decrease, we found elevated levels of cDC2/cDC3 at the 6-7 month timepoint. Analysis of functional markers on monocytes and DC revealed sustained reduction in program death ligand 1 (PD-L1) expression but increased CD86 expression across almost all cell types examined. Finally, C-reactive protein (CRP) correlated positively to the levels of intermediate monocytes and negatively to the recovery of DC subsets.

Conclusion: By exploring the myeloid compartments, we show here that alterations in the immune landscape remain more than 6 months after severe COVID-19, which could be indicative of ongoing healing and/or persistence of viral antigens.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2023
Keywords
COVID-19; SARS-CoV-2; dendritic cells; monocytes; myeloid compartment
National Category
Immunology in the medical area Neurosciences Infectious Medicine
Identifiers
urn:nbn:se:liu:diva-191933 (URN)10.3389/fimmu.2022.1082912 (DOI)000916124600001 ()
Funder
Swedish Research Council, 201701091Region Östergötland, 10.13039/100016670
Note

Funding: ML SciLifeLab/KAW COVID-19 Research Program, Swedish Research Council [201701091]; COVID-19 ALF (Linkoeping University Hospital Research Fund), Region OEstergoetland ALF Grant [ROE935411]; Regional ALF Grant; Vrinnevi Hospital in Norrkoeping

Available from: 2023-02-24 Created: 2023-02-24 Last updated: 2024-01-17Bibliographically approved
Shankar, E. M., Saeidi, A., Vignesh, R., Velu, V. & Larsson, M. (2017). Understanding Immune Senescence, Exhaustion, and Immune Activation in HIV–Tuberculosis Coinfection. In: Fulop, Tamas; Franceschi, Claudio; Hirokawa, Katsuiku; Pawelec, Graham (Ed.), Handbook of Immunosenescence: Basic Understanding and Clinical Implications: (pp. 1-15). Cham: Springer
Open this publication in new window or tab >>Understanding Immune Senescence, Exhaustion, and Immune Activation in HIV–Tuberculosis Coinfection
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2017 (English)In: Handbook of Immunosenescence: Basic Understanding and Clinical Implications / [ed] Fulop, Tamas; Franceschi, Claudio; Hirokawa, Katsuiku; Pawelec, Graham, Cham: Springer , 2017, p. 1-15Chapter in book (Refereed)
Abstract [en]

Human immunodeficiency virus (HIV) and tuberculosis (TB) coinfection accounts for high rates of global morbidity and mortality. Although the pathogeneses of HIV and Mycobacterium tuberculosis (MTB) infections are different, the coexistence of both the agents will lead to accentuated disease progression in the host. Expression of markers associated with chronic immune activation, exhaustion, and immunosenescence on pathogen-specific CD4+ and CD8+ T cells have been associated with suboptimal immune responses in HIV–TB coinfection. The effect of chronic immune activation, exhaustion, and immunosenescence also appears to extend across distinct sets of immune cells, and hence a wider understanding of the mechanistic aspects underlying these phenomena is urgently required to necessitate the expansion of immune cells with improved functions in HIV–TB coinfection. Furthermore, strategies to cause attrition of immunosenescence and immune activation appear to stem from an improved understanding of senescence signaling.

Place, publisher, year, edition, pages
Cham: Springer, 2017
Keywords
CD38; HIV–TB; Coinfection; Immune exhaustion; Immunosenescence
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:liu:diva-197179 (URN)10.1007/978-3-319-64597-1_131-1 (DOI)9783319645971 (ISBN)
Available from: 2023-08-24 Created: 2023-08-24 Last updated: 2023-10-31Bibliographically approved
Yien Tan, H., Kong Yong, Y., Shankar, E. M., Paukovics, G., Ellegård, R., Larsson, M., . . . Crowe, S. M. (2016). Aberrant Inflammasome Activation Characterizes Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome. Journal of Immunology, 196(10), 4052-4063
Open this publication in new window or tab >>Aberrant Inflammasome Activation Characterizes Tuberculosis-Associated Immune Reconstitution Inflammatory Syndrome
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2016 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 196, no 10, p. 4052-4063Article in journal (Refereed) Published
Abstract [en]

Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) complicates combination antiretroviral therapy (cART) in up to 25% of patients with HIV/TB coinfection. Monocytes and IL-18, a signature cytokine of inflammasome activation, are implicated in TB-IRIS pathogenesis. In this study, we investigated inflammasome activation both pre- and post-cART in TB-IRIS patients. HIV/TB patients exhibited higher proportions of monocytes expressing activated caspase-1 (casp1) pre-cART, compared with HIV patients without TB, and patients who developed TB-IRIS exhibited the greatest increase in casp1 expression. CD64(+) monocytes were a marker of increased casp1 expression. Furthermore, IL-1 beta, another marker of inflammasome activation, was also elevated during TB-IRIS. TB-IRIS patients also exhibited greater upregulation of NLRP3 and AIM2 inflammasome mRNA, compared with controls. Analysis of plasma mitochondrial DNA levels showed that TB-IRIS patients experienced greater cell death, especially pre-cART. Plasma NO levels were lower both pre- and post-cART in TB-IRIS patients, providing evidence of inadequate inflammasome regulation. Plasma IL-18 levels pre-cART correlated inversely with NO levels but positively with monocyte casp1 expression and mitochondrial DNA levels, and expression of IL-18R alpha on CD4(+) T cells and NK cells was higher in TB-IRIS patients, providing evidence that IL-18 is a marker of inflammasome activation. We propose that inflammasome activation in monocytes/macrophages of HIV/TB patients increases with ineffective T cell-dependent activation of monocytes/macrophages, priming them for an excessive inflammatory response after cART is commenced, which is greatest in patients with TB-IRIS.

Place, publisher, year, edition, pages
AMER ASSOC IMMUNOLOGISTS, 2016
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-128934 (URN)10.4049/jimmunol.1502203 (DOI)000375831200008 ()27076678 (PubMedID)
Note

Funding Agencies|University of Malaya; Ministry of Higher Education High Impact Research Grant [UM.C/625/1/HIR/MOHE/MED/01]; University of Malaya Research Grants of the Health and Translational Medicine Research Cluster [RP021A-13HTM, RG448-12HTM]; Research Officer Grant Scheme [BR003-2014]; Australian National Health and Medical Research Council; Swedish Research Council [AI52731]; Swedish Physicians against AIDS Research Foundation; Swedish International Development Cooperation Agency; VINNMER from VINNOVA; Linkoping University Hospital research fund; Governmental Funding of Clinical Research within National Health Service; Swedish Society of Medicine; Victorian Operational Infrastructure Support Program

Available from: 2016-06-09 Created: 2016-06-07 Last updated: 2017-11-30
Crisci, E., Ellegård, R., Nyström, S., Rondahl, E., Serrander, L., Bergström, T., . . . Larsson, M. (2016). Complement opsonization promotes HSV-2 infection of human dendritic cells. Journal of Virology, 90(10), 4939-4950
Open this publication in new window or tab >>Complement opsonization promotes HSV-2 infection of human dendritic cells
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2016 (English)In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 90, no 10, p. 4939-4950Article in journal (Refereed) Published
Abstract [en]

Herpes virus type 2 (HSV2) is one of the most common sexually transmitted infections globally with a very high prevalence in many countries. During HSV2 infection viral particles become coated with complement proteins and antibodies, both existent in the genital fluids, which could influence the activation of the immune responses. In genital mucosa, the primary target cells for HSV2 infection are epithelial cells, but resident immune cells such as dendritic cells (DCs) are also infected. The DCs are the activators of the ensuing immune responses directed against HSV2, and the aim of this study was to examine the effects opsonization of HSV2, either with complement alone or with complement and antibodies, had on the infection of immature DCs and their ability to mount inflammatory and antiviral responses. Complement opsonization of HSV2 enhanced both the direct infection of immature DCs and their production of new infectious viral particles. The enhanced infection required activation of the complement cascade and functional complement receptor 3. Furthermore, HSV2 infection of DCs required endocytosis of viral particles and their delivery into an acid endosomal compartment. The presence of complement in combination with HSV1 or HSV2 specific antibodies more or less abolished the HSV2 infection of DCs.Our results clearly demonstrate the importance of studying HSV2 infection under conditions that ensue in vivo, i.e. when the virions are covered in complement fragments and complement fragments and antibodies, as this will shape the infection and the subsequent immune response and needs to be further elucidated.

IMPORTANCE: During HSV2 infection viral particles should become coated with complement proteins and antibodies, both existent in the genital fluids, which could influence the activation of the immune responses. The dendritic cells are the activators of the immune responses directed against HSV2, and the aim of this study was to examine the effects of complement alone or complement and antibodies, on the HSV2 infection of dendritic cells and their ability to mount inflammatory and antiviral responses.Our results demonstrate that the presence of antibodies and complement in the genital environment can influence HSV2 infection under in vitro conditions that reflect the in vivo situation. We believe that our findings are highly relevant for the understanding of HSV2 pathogenesis.

Place, publisher, year, edition, pages
American society of microbiology, 2016
Keywords
HSV2 infection, dendritic cells, complement, antibodies
National Category
Infectious Medicine Microbiology in the medical area
Identifiers
urn:nbn:se:liu:diva-126480 (URN)10.1128/JVI.00224-16 (DOI)000375126100009 ()26937039 (PubMedID)
Note

Funding agencies: Swedish Research Council [AI52731]; Swedish Physicians Against AIDS Research Foundation; Swedish International Development Cooperation Agency; SIDA SARC; VINNMER for Vinnova; Linkoping University Hospital Research Fund; Swedish Society of Medicine; Swedis

Available from: 2016-03-29 Created: 2016-03-29 Last updated: 2021-12-29
Saeidi, A., Ellegård, R., Yong, Y. K., Tan, H. Y., Velu, V., Ussher, J. E., . . . Shankar, E. M. (2016). Functional role of mucosal-associated invariant T cells in HIV infection. Journal of Leukocyte Biology, 100(2), 305-314
Open this publication in new window or tab >>Functional role of mucosal-associated invariant T cells in HIV infection
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2016 (English)In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 100, no 2, p. 305-314Article, review/survey (Refereed) Published
Abstract [en]

MAIT cells represent an evolutionarily conserved, MR1-restricted, innate-like cell subset that express high levels of CD161; have a canonical semi-invariant TCR iV alpha 7.2; and may have an important role in mucosal immunity against various bacterial and fungal pathogens. Mature MAIT cells are CD161(hi)PLZF(hi)IL-18R alpha(+)iV alpha 7.2(+)gamma delta-CD3(+)CD8(+) T cells and occur in the peripheral blood, liver, and mucosa of humans. MAIT cells are activated by a metabolic precursor of riboflavin synthesis presented by MR1 and, therefore, respond to many bacteria and some fungi. Despite their broad antibacterial properties, their functional role in persistent viral infections is poorly understood. Although there is an increasing line of evidence portraying the depletion of MAIT cells in HIV disease, the magnitude and the potential mechanisms underlying such depletion remain unclear. Recent studies suggest that MAIT cells are vulnerable to immune exhaustion as a consequence of HIV and hepatitis C virus infections and HIV/tuberculosis coinfections. HIV infection also appears to cause functional depletion of MAIT cells resulting from abnormal expression of T-bet and EOMES, and effective ART is unable to completely salvage functional MAIT cell loss. Depletion and exhaustion of peripheral MAIT cells may affect mucosal immunity and could increase susceptibility to opportunistic infections during HIV infection. Here, we review some of the important mechanisms associated with depletion and functional loss of MAIT cells and also suggest potential immunotherapeutic strategies to restore MAIT cell functions, including the use of IL-7 to restore effector functions in HIV disease.

Place, publisher, year, edition, pages
FEDERATION AMER SOC EXP BIOL, 2016
Keywords
CD8(+) T cells; cytotoxicity; exhaustion; PD-1; TCR iV alpha 7.2
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:liu:diva-130371 (URN)10.1189/jlb.4RU0216-084R (DOI)000379738600006 ()27256572 (PubMedID)
Note

Funding Agencies|University of Malaya; Ministry of Higher Education [UM.C/625/1/HIR/MOHE/MED/01]; University of Malaya [RP021A-13HTM, RG448-12HTM]; Swedish Research Council [AI52731]; Swedish Physicians Against AIDS Research Foundation; Swedish International Development Cooperation Agency; VINNMER from VINNOVA; Linkoping University Hospital; National Health Service; Swedish Society of Medicine; U.S. National Institutes of Health National Institute of Allergy and Infectious Diseases [1U19AI109633-01]; [BR003-2014]

Available from: 2016-08-15 Created: 2016-08-05 Last updated: 2018-01-10
Kuninty, P. R., Bojmar, L., Tjomsland, V., Larsson, M., Storm, G., Östman, A., . . . Prakash, J. (2016). MicroRNA-199a and -214 as potential therapeutic targets in pancreatic stellate cells in pancreatic tumor. Oncotarget, 7(13), 16396-16408
Open this publication in new window or tab >>MicroRNA-199a and -214 as potential therapeutic targets in pancreatic stellate cells in pancreatic tumor
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2016 (English)In: Oncotarget, E-ISSN 1949-2553, Vol. 7, no 13, p. 16396-16408Article in journal (Refereed) Published
Abstract [en]

Pancreatic stellate cells (PSCs) are the key precursor cells for cancer-associated fibroblasts (CAFs) in pancreatic tumor stroma. Although depletion of tumor stroma is debatable, attenuation of PSC activity is still an interesting strategy to treat pancreatic cancer. In this study, we explored miRNA as therapeutic targets in tumor stroma and found miR-199a-3p and miR-214-3p induced in patient-derived pancreatic CAFs as well as in TGF-β-activated human PSCs (hPSCs). Inhibition of miR-199a or miR-214 using their hairpin inhibitors in hPSCs significantly inhibited their TGFβ-induced differentiation (gene and protein levels of α-SMA, Collagen, PDGFβR), migration and proliferation. Furthermore, heterospheroids of Panc-1 and hPSCs were prepared, which attained smaller size when hPSCs were transfected with anti-miR-199a or -214 than those transfected with control anti-miR. The conditioned medium obtained from TGFβ-activated hPSCs induced tumor cell proliferation and endothelial cell tube formation, but these effects were abrogated when hPSCs were transfected with anti-miR-199a or miR-214. Moreover, IPA analyses revealed signaling pathways related to miR-199a (TP53, mTOR, Smad1) and miR-214 (PTEN, Bax, ING4). Taken together, this study reveals miR-199a-3p and miR-214-3p as major regulators of PSC activation and PSC-induced pro-tumoral effects, representing them as key therapeutic targets in PSCs in pancreatic cancer.

Place, publisher, year, edition, pages
Impact press, 2016
National Category
Cancer and Oncology Cell and Molecular Biology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
urn:nbn:se:liu:diva-122828 (URN)10.18632/oncotarget.7651 (DOI)000375692900085 ()
Note

Funding agencies: Swedish Research Council, Stockholm, Sweden [K7/60501283]

Vid tiden för disputationen förelåg publikationen endast som manuskript

Available from: 2015-11-26 Created: 2015-11-26 Last updated: 2024-01-17
Barathan, M., Mohamed, R., Vadivelu, J., Chang, L. Y., Saeidi, A., Yong, Y. K., . . . Shankar, E. M. (2016). Peripheral loss of CD8(+)CD161(++)TCRV7 center dot 2(+) mucosal-associated invariant T cells in chronic hepatitis C virus-infected patients. European Journal of Clinical Investigation, 46(2), 170-180
Open this publication in new window or tab >>Peripheral loss of CD8(+)CD161(++)TCRV7 center dot 2(+) mucosal-associated invariant T cells in chronic hepatitis C virus-infected patients
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2016 (English)In: European Journal of Clinical Investigation, ISSN 0014-2972, E-ISSN 1365-2362, Vol. 46, no 2, p. 170-180Article in journal (Refereed) Published
Abstract [en]

BackgroundMucosal-associated invariant T (MAIT) cells play an important role in innate host defence. MAIT cells appear to undergo exhaustion and are functionally weakened in chronic viral infections. However, their role in chronic hepatitis C virus (HCV) infection remains unclear. Materials and methodsWe investigated the frequency of CD8(+)CD161(++)TCR V7.2(+) MAIT cells in a cross-sectional cohort of chronic HCV-infected patients (n = 25) and healthy controls (n = 25). Peripheral blood mononuclear cells were investigated for circulating MAIT cell frequency, liver-homing (CCR5 and CD103), biomarkers of immune exhaustion (PD-1, TIM-3 and CTLA-4), chronic immune activation (CD38 and HLA-DR), and immunosenescence (CD57) by flow cytometry. ResultsThe frequency of MAIT cells was significantly decreased, and increased signs of immune exhaustion and chronic immune activation were clearly evident on MAIT cells of HCV-infected patients. Decrease of CCR5 on circulating MAIT cells is suggestive of their peripheral loss in chronic HCV-infected patients. MAIT cells also showed significantly increased levels of HLA-DR, CD38, PD-1, TIM-3 and CTLA-4, besides CD57 in chronic HCV disease. ConclusionsImmune exhaustion and senescence of CD8(+)CD161(++)TCR V7.2(+) MAIT cells could contribute to diminished innate defence attributes likely facilitating viral persistence and HCV disease progression.

Place, publisher, year, edition, pages
WILEY-BLACKWELL, 2016
Keywords
CD38; exhaustion; HCV infection; MAIT cells; PD-1; TCRV alpha 7.2
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-125301 (URN)10.1111/eci.12581 (DOI)000368689100007 ()26681320 (PubMedID)
Note

Funding Agencies|High Impact Research (HIR), University of Malaya [UM.C.625/1/HIR/139]; University Malaya Fellowship Scheme [AI52731]; Swedish Research Council; Swedish Physicians against AIDS Research Foundation; Swedish International Development Cooperation Agency; SIDA SARC; VINNMER for Vinnova; Linkoping University Hospital Research Fund; CALF; Swedish Society of Medicine

Available from: 2016-02-24 Created: 2016-02-19 Last updated: 2017-11-30
Saeidi, A., Tien Tien, V. L., Al-Batran, R., Al-Darraji, H. A., Tan, H. Y., Yong, Y. K., . . . Shankar, E. M. (2015). Attrition of TCR Va7.2+CD161++ MAIT Cells in HIV-Tuberculosis Co-Infection Is Associated with Elevated Levels of PD-1 Expression. PLOS ONE, 10(4), e0124659
Open this publication in new window or tab >>Attrition of TCR Va7.2+CD161++ MAIT Cells in HIV-Tuberculosis Co-Infection Is Associated with Elevated Levels of PD-1 Expression
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2015 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 10, no 4, p. e0124659-Article in journal (Refereed) Published
Abstract [en]

Mucosal-associated invariant T (MAIT) cells are evolutionarily conserved antimicrobial MR1-restricted CD8+ T cells co-expressing the semi-invariant TCR V alpha 7.2, and are numerous in the blood and mucosal tissues of humans. MAIT cells appear to undergo exhaustion in chronic viral infections. However, their role in human immunodeficiency virus type 1 (HIV1) mono-infection and HIV/tuberculosis (TB) co-infection have seldom been elaborately investigated. We conducted a cross-sectional study to investigate the frequencies and phenotypes of CD161++ CD8+ T cells among anti-retroviral therapy (ART)/anti-TB therapy (ATT) treatment-naive HIV/TB co-infected, ART/TB treated HIV/TB co-infected, ART naive HIV-infected, ART-treated HIV-infected patients, and HIV negative healthy controls (HCs) by flow cytometry. Our data revealed that the frequency of MAIT cells was severely depleted in HIV mono-and HIV/TB co-infections. Further, PD-1 expression on MAIT cells was significantly increased in HIV mono-and HIV-TB co-infected patients. The frequency of MAIT cells did not show any significant increase despite the initiation of ART and/or ATT. Majority of the MAIT cells in HCs showed a significant increase in CCR6 expression as compared to HIV/TB co-infections. No marked difference was seen with expressions of chemokine co-receptor CCR5 and CD103 among the study groups. Decrease of CCR6 expression appears to explain why HIV-infected patients display weakened mucosal immune responses.

Place, publisher, year, edition, pages
Public Library of Science, 2015
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-118050 (URN)10.1371/journal.pone.0124659 (DOI)000353211700114 ()25894562 (PubMedID)
Note

Funding Agencies|High Impact Research [UM.C/625/1/HIR/MOHE/MED/014]; University of Malaya Research of the Health and Translational Medicine Research Cluster [RP021A-13HTM, RG448-12HTM]; Swedish Research Council [AI52731]; Swedish Physicians against AIDS Research Foundation; Swedish International Development Cooperation Agency; SIDA SARC; VINNMER for Vinnova; Linkoping University Hospital Research Fund; CALF; Swedish Society of Medicine

Available from: 2015-05-20 Created: 2015-05-20 Last updated: 2021-06-14
Barathan, M., Gopal, K., Mohamed, R., Ellegård, R., Saeidi, A., Vadivelu, J., . . . Shankar, E. M. (2015). Chronic hepatitis C virus infection triggers spontaneous differential expression of biosignatures associated with T cell exhaustion and apoptosis signaling in peripheral blood mononucleocytes. Apoptosis (London), 20(4), 466-480
Open this publication in new window or tab >>Chronic hepatitis C virus infection triggers spontaneous differential expression of biosignatures associated with T cell exhaustion and apoptosis signaling in peripheral blood mononucleocytes
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2015 (English)In: Apoptosis (London), ISSN 1360-8185, E-ISSN 1573-675X, Vol. 20, no 4, p. 466-480Article in journal (Refereed) Published
Abstract [en]

Persistent hepatitis C virus (HCV) infection appears to trigger the onset of immune exhaustion to potentially assist viral persistence in the host, eventually leading to hepatocellular carcinoma. The role of HCV on the spontaneous expression of markers suggestive of immune exhaustion and spontaneous apoptosis in immune cells of chronic HCV (CHC) disease largely remain elusive. We investigated the peripheral blood mononuclear cells of CHC patients to determine the spontaneous recruitment of cellular reactive oxygen species (cROS), immunoregulatory and exhaustion markers relative to healthy controls. Using a commercial QuantiGenePlex(A (R)) 2.0 assay, we determined the spontaneous expression profile of 80 different pro- and anti-apoptotic genes in persistent HCV disease. Onset of spontaneous apoptosis significantly correlated with the up-regulation of cROS, indoleamine 2,3-dioxygenase (IDO), cyclooxygenase-2/prostaglandin H synthase (COX-2/PGHS), Foxp3, Dtx1, Blimp1, Lag3 and Cd160. Besides, spontaneous differential surface protein expression suggestive of T cell inhibition viz., TRAIL, TIM-3, PD-1 and BTLA on CD4+ and CD8+ T cells, and CTLA-4 on CD4+ T cells was also evident. Increased up-regulation of Tnf, Tp73, Casp14, Tnfrsf11b, Bik and Birc8 was observed, whereas FasLG, Fas, Ripk2, Casp3, Dapk1, Tnfrsf21, and Cflar were moderately up-regulated in HCV-infected subjects. Our observation suggests the spontaneous onset of apoptosis signaling and T cell exhaustion in chronic HCV disease.

Place, publisher, year, edition, pages
Springer Verlag (Germany), 2015
Keywords
Apoptosis; Caspase; Hepatitis C; Spontaneous immune exhaustion; TRAIL
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-116813 (URN)10.1007/s10495-014-1084-y (DOI)000350669500005 ()25577277 (PubMedID)
Note

Funding Agencies|High Impact Research, University of Malaya [UM.C.625/1/HIR/139]; HIRG-MOHE Grant of University of Malaya [A000003-50001]; Swedish Research Council [AI52731]; Swedish Physicians against AIDS Research Foundation; Swedish International Development Cooperation Agency; SIDA SARC; VINNMER for Vinnova; Linkoping University Hospital Research Fund; CALF; Swedish Society of Medicine; University of Malaya Research Grant (UMRG) of the Health and Translational Medicine Research Cluster, University of Malaya [RG448-12HTM]

Available from: 2015-04-07 Created: 2015-04-07 Last updated: 2017-12-04
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ORCID iD: ORCID iD iconorcid.org/0000-0002-4524-0177

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