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CD161+ MAIT cells are severely reduced in peripheral blood and lymph nodes of HIV-infected individuals independently of disease progression.

ABSTRACT: Mucosal-associated invariant T (MAIT) cells are characterized by the combined expression of the semi-invariant T cell receptor (TCR) V?7.2, the lectin receptor CD161, as well as IL-18R, and play an important role in antibacterial host defense of the gut. The current study characterized CD161(+) MAIT and CD161-TCRV?7.2(+) T cell subsets within a large cohort of HIV patients with emphasis on patients with slow disease progression and elite controllers. Mononuclear cells from blood and lymph node samples as well as plasma from 63 patients and 26 healthy donors were analyzed by multicolor flow cytometry and ELISA for IL-18, sCD14 and sCD163. Additionally, MAIT cells were analyzed after in vitro stimulation with different cytokines and/or fixed E.coli. Reduced numbers of CD161(+) MAIT cells during HIV infection were detectable in the blood and lymph nodes of all patient groups, including elite controllers. CD161+ MAIT cell numbers did not recover even after successful antiretroviral treatment. The loss of CD161(+) MAIT cells was correlated with higher levels of MAIT cell activation; an increased frequency of the CD161-TCRV?7.2(+)T cell subset in HIV infection was observed. In vitro stimulation of MAIT cells with IL-18 and IL-12, IL-7 and fixed E.coli also resulted in a rapid and additive reduction of the MAIT cell frequency defined by CD161, IL-18R and CCR6. In summary, the irreversible reduction of the CD161(+) MAIT cell subset seems to be an early event in HIV infection that is independent of later stages of the disease. This loss appears to be at least partially due to the distinctive vulnerability of MAIT cells to the pronounced stimulation by microbial products and cytokines during HIV-infection.

SUBMITTER: Eberhard JM

PROVIDER: S-EPMC4219715 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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CD161+ MAIT cells are severely reduced in peripheral blood and lymph nodes of HIV-infected individuals independently of disease progression.

Eberhard Johanna Maria JM Hartjen Philip P Kummer Silke S Schmidt Reinhold E RE Bockhorn Maximilian M Lehmann Clara C Balagopal Ashwin A Hauber Joachim J van Lunzen Jan J Schulze zur Wiesch Julian J

PloS one 20141104 11

Mucosal-associated invariant T (MAIT) cells are characterized by the combined expression of the semi-invariant T cell receptor (TCR) Vα7.2, the lectin receptor CD161, as well as IL-18R, and play an important role in antibacterial host defense of the gut. The current study characterized CD161(+) MAIT and CD161-TCRVα7.2(+) T cell subsets within a large cohort of HIV patients with emphasis on patients with slow disease progression and elite controllers. Mononuclear cells from blood and lymph node s ...[more]

PMID: 25369333

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Project description:Both HIV and HCV infections feature increased microbial translocation (MT) and gut dysbiosis that affect immune homeostasis and disease outcome. Given their commitment to antimicrobial mucosal immunity, we investigated mucosal-associated invariant T (MAIT) cells and Vα7.2+CD161- T-cell frequency/function and their possible associations with MT and gut dysbiosis, in chronic HIV and/or HCV infections. We enrolled 56 virally infected (VI) patients (pts): 13 HIV+ on suppressive cART (HIV-RNA < 40cp/ml), 13 HCV+ naive to DAA (direct-acting antiviral) anti-HCV agents; 30 HCV+/HIV+ on suppressive cART and naive to anti-HCV. 13 age-matched healthy controls (HC) were enrolled. For Vα7.2+CD161++ and Vα7.2+CD161-CD8+ T cells we assessed: activation (CD69), exhaustion (PD1/CD39), and cytolytic activity (granzymeB/perforin). Following PMA/ionomycin and Escherichia coli stimulation we measured intracellular IL17/TNFα/IFNγ. Markers of microbial translocation (Plasma LPS, 16S rDNA, EndoCAb and I-FABP) were quantified. In 5 patients per group we assessed stool microbiota composition by 16S targeted metagenomics sequencing (alpha/beta diversity, relative abundance). Compared to controls, virally infected pts displayed significantly lower circulating Vα7.2+CD161++CD8+ MAIT cells (p = 0.001), yet expressed higher perforin (p = 0.004) and granzyme B (p = 0.002) on CD8+ MAIT cells. Upon E. coli stimulation, the residual MAIT cells are less functional particularly those from HIV+/HCV+ patients. Conversely, in virally infected pts, Vα7.2+CD161-CD8+ cells were comparable in frequency, highly activated/exhausted (CD69+: p = 0.002; PD-1+: p = 0.030) and with cytolytic potential (perforin+: p < 0.0001), yet were poorly responsive to ex vivo stimulation. A profound gut dysbiosis characterized virally infected pts, especially HCV+/HIV+ co-infected patients, delineating a Firmicutes-poor/Bacteroidetes-rich microbiota, with significant associations with MAIT cell frequency/function. Irrespective of mono/dual infection, HIV+ and HCV+ patients display depleted, yet activated/cytolytic MAIT cells with reduced ex vivo function, suggesting an impoverished pool, possibly due to continuous bacterial challenge. The MAIT cell ability to respond to bacterial stimulation correlates with the presence of Firmicutes and Bacteroidetes, possibly suggesting an association between gut dysbiosis and MAIT cell function and posing viral-mediated dysbiosis as a potential key player in the hampered anti-bacterial MAIT ability.

Project description:To more fully characterize the burden of Salmonella enterica in bovine peripheral lymph nodes (PLN), PLN (n = 5,450) were collected from healthy cattle at slaughter in 12 commercial abattoirs that slaughtered feedlot-fattened (FF) cattle exclusively (n = 7), cattle removed (or culled) from breeding herds (n = 3), or both FF and cull cattle (n = 2). Qualitative and quantitative methods were used to estimate prevalence and concentration of Salmonella in PLN. Isolates were subjected to a variety of phenotypic, serological, and molecular assays. Overall, Salmonella prevalence in PLN from FF and cull cattle was 7.1 and 1.8%. However, burden varied by season in that observed prevalence in PLN collected in cooler or warmer seasons was 2.4 and 8.2%, respectively. Prevalence in PLN from cull cattle in the southwest region of the US was 2.1 and 1.1% for cool and warm seasons, respectively; however, prevalence in FF PLN was far greater in that it was 6.5 and 31.1%, respectively. Salmonella was recovered from 289 (5.6%) PLN and 2.9% (n = 160) of all PLN tested had quantifiable concentrations that varied from 1.6 to 4.9 log10 colony forming units/PLN. The most common serotypes isolated from PLN were Montevideo (26.9%), Lille (14.9%), Cerro (13.0%), Anatum (12.8%), and Dublin (6.9%). In all, 376 unique isolates were collected from the 289 Salmonella-positive PLN. Antimicrobial susceptibility testing revealed the majority (80.6%) of these isolates were pansusceptible; however, 10.7% of isolates were found to be resistant to two or more antimicrobial classes. We were able to document an observed increased in prevalence of Salmonella in PLN during the warmer season, particularly in FF cattle from the southwest region of the US. The mechanisms underlying the observed association between season, region, and production source have yet to be elucidated. Nevertheless, these findings increase our understanding of the sources of contamination of beef products and shed light on transmission dynamics that may be useful in targeting these sources.

Dataset Information

CD161+ MAIT cells are severely reduced in peripheral blood and lymph nodes of HIV-infected individuals independently of disease progression.

Publications

CD161+ MAIT cells are severely reduced in peripheral blood and lymph nodes of HIV-infected individuals independently of disease progression.

Similar Datasets

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