liu.seSök publikationer i DiVA
Ändra sökning
Länk till posten
Permanent länk

Direktlänk
BETA
Hinkula, Jorma
Alternativa namn
Publikationer (10 of 56) Visa alla publikationer
Patra, H. K., Azharuddin, M., Islam, M. M., Papapavlou, G., Deb, S., Osterrieth, J., . . . Slater, N. K. H. (2019). Rational Nanotoolbox with Theranostic Potential for Medicated Pro-Regenerative Corneal Implants. Advanced Functional Materials, Article ID 1903760.
Öppna denna publikation i ny flik eller fönster >>Rational Nanotoolbox with Theranostic Potential for Medicated Pro-Regenerative Corneal Implants
Visa övriga...
2019 (Engelska)Ingår i: Advanced Functional Materials, ISSN 1616-301X, E-ISSN 1616-3028, artikel-id 1903760Artikel i tidskrift (Refereegranskat) Epub ahead of print
Abstract [en]

Cornea diseases are a leading cause of blindness and the disease burden is exacerbated by the increasing shortage around the world for cadaveric donor corneas. Despite the advances in the field of regenerative medicine, successful transplantation of laboratory‐made artificial corneas is not fully realized in clinical practice. The causes of failure of such artificial corneal implants are multifactorial and include latent infections from viruses and other microbes, enzyme overexpression, implant degradation, extrusion or delayed epithelial regeneration. Therefore, there is an urgent unmet need for developing customized corneal implants to suit the host environment and counter the effects of inflammation or infection, which are able to track early signs of implant failure in situ. This work reports a nanotoolbox comprising tools for protection from infection, promotion of regeneration, and noninvasive monitoring of the in situ corneal environment. These nanosystems can be incorporated within pro‐regenerative biosynthetic implants, transforming them into theranostic devices, which are able to respond to biological changes following implantation.

Ort, förlag, år, upplaga, sidor
John Wiley & Sons, 2019
Nyckelord
herpes simplex virus type 1 (HSV-1), magnetic resonance imaging (MRI), premedicated cornea implants, pro-regeneration, theranostics
Nationell ämneskategori
Mikrobiologi inom det medicinska området
Identifikatorer
urn:nbn:se:liu:diva-159097 (URN)10.1002/adfm.201903760 (DOI)000476281800001 ()2-s2.0-85069940064 (Scopus ID)
Anmärkning

Funding agencies: EU H2020 Marie Sklodowska-Curie Individual Fellowship [706694]; MIIC Strategic Postdoc Grant; MIIC Seed Grant at Linkoping University (LiU), Sweden

Tillgänglig från: 2019-07-24 Skapad: 2019-07-24 Senast uppdaterad: 2019-08-23Bibliografiskt granskad
Falkeborn, T., Asahara, N., Hayashi, M., Arai, M., Hinkula, J. & Maltais, A.-K. (2015). Comparison of the mucosal adjuvant Endocine™ with two well-known adjuvants: cholera toxin and alum. Jacobs Journal of Vaccine and Vaccination, 1(1), Article ID 006.
Öppna denna publikation i ny flik eller fönster >>Comparison of the mucosal adjuvant Endocine™ with two well-known adjuvants: cholera toxin and alum
Visa övriga...
2015 (Engelska)Ingår i: Jacobs Journal of Vaccine and Vaccination, ISSN 2381-2664, Vol. 1, nr 1, artikel-id 006Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

To enable efficient mucosal vaccination with split or subunit antigens, an adjuvant is often needed. To date, no mucosal adjuvants are approved for human use, however, there are a variety of mucosal adjuvants in development, including the liposome-based adjuvant Endocine™. The aim of this study was to evaluate split influenza antigens together with Endocine™ and in order to assess the potency of Endocine™, the induction of humoral immune responses were compared to those following influenza vaccination with cholera toxin (CT) or aluminum salt (alum). We show that Endocine™ significantly enhances influenza-specific immune responses in intranasally immunized mice compared to nonadjuvanted vaccine. Furthermore, vaccines adjuvanted with Endocine™ evoked comparable serum IgG and virus neutralizing (VN) antibody titers as nasal vaccines adjuvanted with CT. Compared to parenteral vaccination with alum, Endocine™ triggered significantly higher mucosal and serum IgA titers, and similar VN titers. Taken together, these results support further development of Endocine™ as a mucosal adjuvant and as part of a nasal influenza vaccine candidate.

Ort, förlag, år, upplaga, sidor
Jacobs Publishers, 2015
Nyckelord
Mucosal adjuvant; nasal immunization; vaccine; Endocine; influenza; neutralizing antibodies
Nationell ämneskategori
Klinisk laboratoriemedicin Cell- och molekylärbiologi
Identifikatorer
urn:nbn:se:liu:diva-117979 (URN)
Tillgänglig från: 2015-05-19 Skapad: 2015-05-19 Senast uppdaterad: 2018-01-11Bibliografiskt granskad
Ellegård, R., Crisci, E., Andersson, J., Shankar, E. M., Nyström, S., Hinkula, J. & Larsson, M. (2015). Impaired NK Cell Activation and Chemotaxis toward Dendritic Cells Exposed to Complement-Opsonized HIV-1. Journal of Immunology, 195(4), 1698-1704
Öppna denna publikation i ny flik eller fönster >>Impaired NK Cell Activation and Chemotaxis toward Dendritic Cells Exposed to Complement-Opsonized HIV-1
Visa övriga...
2015 (Engelska)Ingår i: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 195, nr 4, s. 1698-1704Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Mucosa resident dendritic cells (DCs) may represent one of the first immune cells that HIV-1 encounters during sexual transmission. The virions in body fluids can be opsonized with complement factors because of HIV-mediated triggering of the complement cascade, and this appears to influence numerous aspects of the immune defense targeting the virus. One key attribute of host defense is the ability to attract immune cells to the site of infection. In this study, we investigated whether the opsonization of HIV with complement (C-HIV) or a mixture of complement and Abs (CI-HIV) affected the cytokine and chemokine responses generated by DCs, as well as their ability to attract other immune cells. We found that the expression levels of CXCL8, CXCL10, CCL3, and CCL17 were lowered after exposure to either C-HIV or CI-HIV relative to free HIV (F-HIV). DCs exposed to F-HIV induced higher cell migration, consisting mainly of NK cells, compared with opsonized virus, and the chemotaxis of NK cells was dependent on CCL3 and CXCL10. NK cell exposure to supernatants derived from HIV-exposed DCs showed that F-HIV induced phenotypic activation (e.g., increased levels of TIM3, CD69, and CD25) and effector function (e.g., production of IFN gamma and killing of target cells) in NK cells, whereas C-HIV and CI-HIV did not. The impairment of NK cell recruitment by DCs exposed to complement-opsonized HIV and the lack of NK activation may contribute to the failure of innate immune responses to control HIV at the site of initial mucosa infection.

Ort, förlag, år, upplaga, sidor
American Association of Immunologists, 2015
Nationell ämneskategori
Klinisk medicin
Identifikatorer
urn:nbn:se:liu:diva-121313 (URN)10.4049/jimmunol.1500618 (DOI)000360013200039 ()26157174 (PubMedID)
Anmärkning

Funding Agencies|Swedish Research Council; Swedish Physicians against AIDS Research Foundation [AI52731]; Swedish International Development Cooperation Agency/Swedish Agency for Research Cooperation with Developing Countries-Special Assistant; VINNMER for Vinnova; Linkoping University Hospital Research Fund; central regional agreement on medical training and clinical research (CALF) between Ostergotland County Council and Linkoping University; Swedish Society of Medicine; High Impact Research; University of Malaya [UM.C.625/1/HIR/139]

Tillgänglig från: 2015-09-16 Skapad: 2015-09-14 Senast uppdaterad: 2018-09-28
Ellegård, R., Crisci, E., Burgener, A., Sjöwall, C., Birse, K., Westmacott, G., . . . Larsson, M. (2014). Complement Opsonization of HIV-1 Results in Decreased Antiviral and Inflammatory Responses in Immature Dendritic Cells via CR3. Journal of Immunology, 193(9), 4590-4601
Öppna denna publikation i ny flik eller fönster >>Complement Opsonization of HIV-1 Results in Decreased Antiviral and Inflammatory Responses in Immature Dendritic Cells via CR3
Visa övriga...
2014 (Engelska)Ingår i: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 193, nr 9, s. 4590-4601Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Immature dendritic cells (iDCs) in genital and rectal mucosa may be one of the first cells to come into contact with HIV-1 during sexual transmission of virus. HIV-1 activates the host complement system, which results in opsonization of virus by inactivated complement fragments, for example, iC3b. We investigated antiviral and inflammatory responses induced in human iDCs after exposure to free HIV-1 (F-HIV), complement-opsonized HIV-1 (C-HIV), and complement and Ab-opsonized HIV-1 (CI-HIV). F-HIV gave rise to a significantly higher expression of antiviral factors such as IFN-beta, myxovirus resistance protein A, and IFN-stimulated genes, compared with C-HIV and CI-HIV. Additionally, F-HIV induced inflammatory factors such as IL-1 beta, IL-6, and TNF-alpha, whereas these responses were weakened or absent after C-HIV or CI-HIV exposure. The responses induced by F-HIV were TLR8-dependent with subsequent activation of IFN regulatory factor 1, p38, ERK, PI3K, and NF-kappa B pathways, whereas these responses were not induced by C-HIV, which instead induced activation of IFN regulatory factor 3 and Lyn. This modulation of TLR8 signaling was mediated by complement receptor 3 and led to enhanced infection. The impact that viral hijacking of the complement system has on iDC function could be an important immune evasion mechanism used by HIV-1 to establish infection in the host.

Ort, förlag, år, upplaga, sidor
American Association of Immunologists, 2014
Nationell ämneskategori
Medicinska och farmaceutiska grundvetenskaper
Identifikatorer
urn:nbn:se:liu:diva-112625 (URN)10.4049/jimmunol.1401781 (DOI)000344079500033 ()25252956 (PubMedID)
Anmärkning

Funding Agencies|Swedish Research Council; Swedish Physicians against AIDS Research Foundation; Swedish International Development Cooperation Agency; VINNMER for Vinnova; Linkoping University Hospital Research Fund Grant C-ALF; Swedish Society of Medicine; National Cancer Institute, National Institutes of Health [HHSN261200800001E]; Swedish Society for Medical Research

Tillgänglig från: 2014-12-08 Skapad: 2014-12-05 Senast uppdaterad: 2018-09-28Bibliografiskt granskad
Oynebraten, I., Hinkula, J., Fredriksen, A. B. & Bogen, B. (2014). Increased Generation of HIV-1 gp120-Reactive CD8(+) T Cells by a DNA Vaccine Construct Encoding the Chemokine CCL3. PLoS ONE, 9(8), e104814
Öppna denna publikation i ny flik eller fönster >>Increased Generation of HIV-1 gp120-Reactive CD8(+) T Cells by a DNA Vaccine Construct Encoding the Chemokine CCL3
2014 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 8, s. e104814-Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

DNA vaccines based on subunits from pathogens have several advantages over other vaccine strategies. DNA vaccines can easily be modified, they show good safety profiles, are stable and inexpensive to produce, and the immune response can be focused to the antigen of interest. However, the immunogenicity of DNA vaccines which is generally quite low needs to be improved. Electroporation and co-delivery of genetically encoded immune adjuvants are two strategies aiming at increasing the efficacy of DNA vaccines. Here, we have examined whether targeting to antigen-presenting cells (APC) could increase the immune response to surface envelope glycoprotein (Env) gp120 from Human Immunodeficiency Virus type 1 (HIV- 1). To target APC, we utilized a homodimeric vaccine format denoted vaccibody, which enables covalent fusion of gp120 to molecules that can target APC. Two molecules were tested for their efficiency as targeting units: the antibody-derived single chain Fragment variable (scFv) specific for the major histocompatilibility complex (MHC) class II I-E molecules, and the CC chemokine ligand 3 (CCL3). The vaccines were delivered as DNA into muscle of mice with or without electroporation. Targeting of gp120 to MHC class II molecules induced antibodies that neutralized HIV-1 and that persisted for more than a year after one single immunization with electroporation. Targeting by CCL3 significantly increased the number of HIV-1 gp120-reactive CD8(+) T cells compared to non-targeted vaccines and gp120 delivered alone in the absence of electroporation. The data suggest that chemokines are promising molecular adjuvants because small amounts can attract immune cells and promote immune responses without advanced equipment such as electroporation.

Ort, förlag, år, upplaga, sidor
Public Library of Science, 2014
Nationell ämneskategori
Klinisk medicin
Identifikatorer
urn:nbn:se:liu:diva-110974 (URN)10.1371/journal.pone.0104814 (DOI)000341017000062 ()25122197 (PubMedID)
Anmärkning

Funding Agencies|Research Council of Norway; Odd Fellow

Tillgänglig från: 2014-10-01 Skapad: 2014-10-01 Senast uppdaterad: 2017-12-05
Timpka, T., Spreco, A., Gursky, E., Eriksson, O., Dahlström, Ö., Strömgren, M., . . . Holm, E. (2014). Intentions to perform non-pharmaceutical protective behaviors during influenza outbreaks in Sweden: a cross-sectional study following a mass vaccination campaign. PLoS ONE, 9(3), e91060
Öppna denna publikation i ny flik eller fönster >>Intentions to perform non-pharmaceutical protective behaviors during influenza outbreaks in Sweden: a cross-sectional study following a mass vaccination campaign
Visa övriga...
2014 (Engelska)Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 3, s. e91060-Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Failure to incorporate the beliefs and attitudes of the public into theoretical models of preparedness has been identified as a weakness in strategies to mitigate infectious disease outbreaks. We administered a cross-sectional telephone survey to a representative sample (n = 443) of the Swedish adult population to examine whether self-reported intentions to improve personal hygiene and increase social distancing during influenza outbreaks could be explained by trust in official information, self-reported health (SF-8), sociodemographic factors, and determinants postulated in protection motivation theory, namely threat appraisal and coping appraisal. The interviewees were asked to make their appraisals for two scenarios: a) an influenza with low case fatality and mild lifestyle impact; b) severe influenza with high case fatality and serious disturbances of societal functions. Every second respondent (50.0%) reported high trust in official information about influenza. The proportion that reported intentions to take deliberate actions to improve personal hygiene during outbreaks ranged between 45–85%, while less than 25% said that they intended to increase social distancing. Multiple logistic regression models with coping appraisal as the explanatory factor most frequently contributing to the explanation of the variance in intentions showed strong discriminatory performance for staying home while not ill (mild outbreaks: Area under the curve [AUC] 0.85 (95% confidence interval 0.82;0.89), severe outbreaks AUC 0.82 (95% CI 0.77;0.85)) and acceptable performance with regard to avoiding public transportation (AUC 0.78 (0.74;0.82), AUC 0.77 (0.72;0.82)), using handwash products (AUC 0.70 (0.65;0.75), AUC 0.76 (0.71;0.80)), and frequently washing hands (AUC 0.71 (0.66;0.76), AUC 0.75 (0.71;0.80)). We conclude that coping appraisal was the explanatory factor most frequently included in statistical models explaining self-reported intentions to carry out non-pharmaceutical health actions in the Swedish outlined context, and that variations in threat appraisal played a smaller role in these models despite scientific uncertainties surrounding a recent mass vaccination campaign.

Ort, förlag, år, upplaga, sidor
Public Library of Science, 2014
Nationell ämneskategori
Hälsovetenskaper
Identifikatorer
urn:nbn:se:liu:diva-105029 (URN)10.1371/journal.pone.0091060 (DOI)000332485800091 ()
Tillgänglig från: 2014-03-06 Skapad: 2014-03-06 Senast uppdaterad: 2018-04-07Bibliografiskt granskad
Maltais, A.-K., Stittelaar, K. J., Veldhuis Kroeze, E. J., van Amerongen, G., Dijkshoorn, M. L., Krestin, G. P., . . . Osterhaus, A. D. (2014). Intranasally administered Endocine™ formulated 2009 pandemic influenza H1N1 vaccine induces broad specific antibody responses and confers protection in ferrets. Vaccine, 32(26), 3307-15
Öppna denna publikation i ny flik eller fönster >>Intranasally administered Endocine™ formulated 2009 pandemic influenza H1N1 vaccine induces broad specific antibody responses and confers protection in ferrets
Visa övriga...
2014 (Engelska)Ingår i: Vaccine, ISSN 0264-410X, E-ISSN 1873-2518, Vol. 32, nr 26, s. 3307-15Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Influenza is a contagious respiratory disease caused by an influenza virus. Due to continuous antigenic drift of seasonal influenza viruses, influenza vaccines need to be adjusted before every influenza season. This allows annual vaccination with multivalent seasonal influenza vaccines, recommended especially for high-risk groups. There is a need for a seasonal influenza vaccine that induces broader and longer lasting protection upon easy administration. Endocine™ is a lipid-based mucosal adjuvant composed of endogenous lipids found ubiquitously in the human body. Intranasal administration of influenza antigens mixed with this adjuvant has been shown to induce local and systemic immunity as well as protective efficacy against homologous influenza virus challenge in mice. Here we used ferrets, an established animal model for human influenza virus infections, to further investigate the potential of Endocine™ as an adjuvant. Intranasal administration of inactivated pandemic H1N1/California/2009 split antigen or whole virus antigen mixed with Endocine™ induced high levels of serum hemagglutination inhibition (HI) and virus neutralization (VN) antibody titers that were also cross reactive against distant swine viruses of the same subtype. HI and VN antibody titers were already demonstrated after a single nasal immunization. Upon intratracheal challenge with a homologous challenge virus (influenza virus H1N1/The Netherlands/602/2009) immunized ferrets were fully protected from virus replication in the lungs and largely protected against body weight loss, virus replication in the upper respiratory tract and pathological changes in the respiratory tract. Endocine™ formulated vaccines containing split antigen induced higher HI and VN antibody responses and better protection from body weight loss and virus shedding in the upper respiratory tract than the Endocine™ formulated vaccine containing whole virus antigen.

Nationell ämneskategori
Medicinska och farmaceutiska grundvetenskaper Klinisk medicin
Identifikatorer
urn:nbn:se:liu:diva-106769 (URN)10.1016/j.vaccine.2014.03.061 (DOI)000336872500028 ()24690149 (PubMedID)2-s2.0-84900393484 (Scopus ID)
Tillgänglig från: 2014-05-22 Skapad: 2014-05-22 Senast uppdaterad: 2019-02-01
Timpka, T., Spreco, A., Dahlström, Ö., Eriksson, O., Gursky, E., Ekberg, J., . . . Holm, E. (2014). Performance of eHealth data sources in local influenza surveillance: a 5-year open cohort study. Journal of Medical Internet Research, 16(4), e116
Öppna denna publikation i ny flik eller fönster >>Performance of eHealth data sources in local influenza surveillance: a 5-year open cohort study
Visa övriga...
2014 (Engelska)Ingår i: Journal of Medical Internet Research, ISSN 1438-8871, E-ISSN 1438-8871, Vol. 16, nr 4, s. e116-Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

BACKGROUND: There is abundant global interest in using syndromic data from population-wide health information systems--referred to as eHealth resources--to improve infectious disease surveillance. Recently, the necessity for these systems to achieve two potentially conflicting requirements has been emphasized. First, they must be evidence-based; second, they must be adjusted for the diversity of populations, lifestyles, and environments.

OBJECTIVE: The primary objective was to examine correlations between data from Google Flu Trends (GFT), computer-supported telenursing centers, health service websites, and influenza case rates during seasonal and pandemic influenza outbreaks. The secondary objective was to investigate associations between eHealth data, media coverage, and the interaction between circulating influenza strain(s) and the age-related population immunity.

METHODS: An open cohort design was used for a five-year study in a Swedish county (population 427,000). Syndromic eHealth data were collected from GFT, telenursing call centers, and local health service website visits at page level. Data on mass media coverage of influenza was collected from the major regional newspaper. The performance of eHealth data in surveillance was measured by correlation effect size and time lag to clinically diagnosed influenza cases.

RESULTS: Local media coverage data and influenza case rates showed correlations with large effect sizes only for the influenza A (A) pH1N1 outbreak in 2009 (r=.74, 95% CI .42-.90; P<.001) and the severe seasonal A H3N2 outbreak in 2011-2012 (r=.79, 95% CI .42-.93; P=.001), with media coverage preceding case rates with one week. Correlations between GFT and influenza case data showed large effect sizes for all outbreaks, the largest being the seasonal A H3N2 outbreak in 2008-2009 (r=.96, 95% CI .88-.99; P<.001). The preceding time lag decreased from two weeks during the first outbreaks to one week from the 2009 A pH1N1 pandemic. Telenursing data and influenza case data showed correlations with large effect sizes for all outbreaks after the seasonal B and A H1 outbreak in 2007-2008, with a time lag decreasing from two weeks for the seasonal A H3N2 outbreak in 2008-2009 (r=.95, 95% CI .82-.98; P<.001) to none for the A p H1N1 outbreak in 2009 (r=.84, 95% CI .62-.94; P<.001). Large effect sizes were also observed between website visits and influenza case data.

CONCLUSIONS: Correlations between the eHealth data and influenza case rates in a Swedish county showed large effect sizes throughout a five-year period, while the time lag between signals in eHealth data and influenza rates changed. Further research is needed on analytic methods for adjusting eHealth surveillance systems to shifts in media coverage and to variations in age-group related immunity between virus strains. The results can be used to inform the development of alert-generating eHealth surveillance systems that can be subject for prospective evaluations in routine public health practice.

Ort, förlag, år, upplaga, sidor
Journal of Medical Internet Research, 2014
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-106758 (URN)10.2196/jmir.3099 (DOI)000336501600017 ()24776527 (PubMedID)
Tillgänglig från: 2014-05-21 Skapad: 2014-05-21 Senast uppdaterad: 2018-04-07Bibliografiskt granskad
Timpka, T., Spreco, A., Eriksson, O., Dahlström, Ö., Gursky, E. A., Stromgren, M., . . . Eriksson, H. (2014). Predictive performance of telenursing complaints in influenza surveillance: a prospective cohort study in Sweden. Eurosurveillance, 19(46), 24-32
Öppna denna publikation i ny flik eller fönster >>Predictive performance of telenursing complaints in influenza surveillance: a prospective cohort study in Sweden
Visa övriga...
2014 (Engelska)Ingår i: Eurosurveillance, ISSN 1025-496X, E-ISSN 1560-7917, Vol. 19, nr 46, s. 24-32Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Syndromic data sources have been sought to improve the timely detection of increased influenza transmission. This study set out to examine the prospective performance of telenursing chief complaints in predicting influenza activity. Data from two influenza seasons (2007/08 and 2008/09) were collected in a Swedish county (population 427,000) to retrospectively determine which grouping of telenursing chief complaints had the largest correlation with influenza case rates. This grouping was prospectively evaluated in the three subsequent seasons. The best performing telenursing complaint grouping in the retrospective algorithm calibration was fever (child, adult) and syncope (r=0.66; pless than0.001). In the prospective evaluation, the performance of 14-day predictions was acceptable for the part of the evaluation period including the 2009 influenza pandemic (area under the curve (AUC)=0.84; positive predictive value (PPV)=0.58), while it was strong (AUC=0.89; PPV=0.93) for the remaining evaluation period including only influenza winter seasons. We recommend the use of telenursing complaints for predicting winter influenza seasons. The method requires adjustments when used during pandemics.

Ort, förlag, år, upplaga, sidor
EUR CENTRE DIS PREVENTION and CONTROL, 2014
Nationell ämneskategori
Medicinska och farmaceutiska grundvetenskaper Matematik Klinisk medicin
Identifikatorer
urn:nbn:se:liu:diva-113057 (URN)000345424100004 ()
Anmärkning

Funding Agencies|Swedish Civil Contingencies Agency [2010-2788]; Swedish Science Council [2008-5252]; Swedish Governmental Agency for Innovations (VINNOVA) [2011-03231]

Tillgänglig från: 2015-01-09 Skapad: 2015-01-08 Senast uppdaterad: 2018-04-07
Tjomsland, V., Ellegård, R., Kjölhede, P., Borendal Wodlin, N., Hinkula, J., Lifson, J. & Larsson, M. (2013). Blocking of integrins inhibits HIV-1 infection of human cervical mucosa immune cells with free and complement-opsonized virions. European Journal of Immunology, 43(9), 2361-2372
Öppna denna publikation i ny flik eller fönster >>Blocking of integrins inhibits HIV-1 infection of human cervical mucosa immune cells with free and complement-opsonized virions
Visa övriga...
2013 (Engelska)Ingår i: European Journal of Immunology, ISSN 0014-2980, E-ISSN 1521-4141, Vol. 43, nr 9, s. 2361-2372Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

The initial interaction between HIV-1 and the host occurs at the mucosa during sexual intercourse. In cervical mucosa, HIV-1 exists both as free and opsonized virions and this might influence initial infection. We used cervical explants to study HIV-1 transmission, the effects of opsonization on infectivity, and how infection can be prevented. Complement opsonization enhanced HIV-1 infection of dendritic cells (DCs) compared with that by free HIV-1, but this increased infection was not observed with CD4+ T cells. Blockage of the α4-, β7-, and β1-integrins significantly inhibited HIV-1 infection of both DCs and CD4+ T cells. We found a greater impairment of HIV-1 infection in DCs for complement-opsonized virions compared with that of free virions when αM/β2- and α4-integrins were blocked. Blocking the C-type lectin receptor macrophage mannose receptor (MMR) inhibited infection of emigrating DCs but had no effect on CD4+ T-cell infection. We show that blocking of integrins decreases the HIV-1 infection of both mucosal DCs and CD4+ T cells emigrating from the cervical tissues. These findings may provide the basis of novel microbicidal strategies that may help limit or prevent initial infection of the cervical mucosa, thereby reducing or averting systemic HIV-1 infection.

Nyckelord
CD4+ T cells, Complement system, DCs, HIV, Integrins
Nationell ämneskategori
Medicin och hälsovetenskap
Identifikatorer
urn:nbn:se:liu:diva-97646 (URN)10.1002/eji.201243257 (DOI)000327819200016 ()23686382 (PubMedID)
Tillgänglig från: 2013-09-19 Skapad: 2013-09-19 Senast uppdaterad: 2019-06-28
Organisationer

Sök vidare i DiVA

Visa alla publikationer