liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
HIV Interferes with the Dendritic Cell-T Cell Axis of Macrophage Activation by Shifting Mycobacterium tuberculosis-Specific CD4 T Cells into a Dysfunctional Phenotype
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Kalmar Cty Hosp, Sweden.
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
Show others and affiliations
2019 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 202, no 3, p. 816-826Article in journal (Refereed) Published
Abstract [en]

HIV coinfection is the greatest risk factor for transition of latent Mycobacterium tuberculosis infection into active tuberculosis (TB). Epidemiological data reveal both the reduction and the impairment of M. tuberculosis-specific CD4 T cells, although the cellular link and actual mechanisms resulting in immune impairment/suppression need further characterization. M. tuberculosis-specific CD4 T cells play a central role in development of protective immunity against TB, in which they participate in the activation of macrophages through the dendritic cell (DC)-T cell axis. Using an in vitro priming system for generating Ag-specific T cells, we explored if HIV-M. tuberculosis-infected (coinfected) human DCs can dysregulate the M. tuberculosis-specific CD4 T cell phenotype and functionality and subsequently mediate the failure to control M. tuberculosis infection in macrophages. After coculture with coinfected DCs, M. tuberculosis Ag-specific CD4 T cells lost their ability to enhance control of M. tuberculosis infection in infected macrophages. Coinfection of DCs reduced proliferation of M. tuberculosis Ag-specific CD4 T cells without affecting their viability, led to increased expression of coinhibitory factors CTLA-4, PD-1, and Blimp-1, and decreased expression of costimulatory molecules CD40L, CD28, and ICOS on the T cells. Expression of the regulatory T cell markers FOXP3 and CD25, together with the immunosuppressive cytokines TGF-beta and IL-10, was also significantly increased by coinfection compared with M. tuberculosis single infection. Our data suggest a pattern in which HIV, through its effect on DCs, impairs the ability of M. tuberculosis-specific CD4 T cells to maintain a latent TB within human macrophages, which could play an early role in the subsequent development of TB.

Place, publisher, year, edition, pages
AMER ASSOC IMMUNOLOGISTS , 2019. Vol. 202, no 3, p. 816-826
National Category
Immunology
Identifiers
URN: urn:nbn:se:liu:diva-154680DOI: 10.4049/jimmunol.1800523ISI: 000456336000021PubMedID: 30593540OAI: oai:DiVA.org:liu-154680DiVA, id: diva2:1292656
Note

Funding Agencies|Swedish Research Council [2017-05617, 348-2013-6588]; Swedish Heart-Lung Foundation [20140578, 2016-0431, 2016-0719]; Stiftelsen Clas Groschinskys Minnesfond; Swedish Society of Medicine Grant [SLS-499971]

Available from: 2019-02-28 Created: 2019-02-28 Last updated: 2019-02-28

Open Access in DiVA

No full text in DiVA

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Singh, Susmita K.Larsson, MarieSchön, ThomasStendahl, OlleBlomgran, Robert
By organisation
Division of Microbiology and Molecular MedicineFaculty of Medicine and Health Sciences
In the same journal
Journal of Immunology
Immunology

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 59 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf