Department of Microbiology and Physiological Systems
Bacteriology | Immunity | Immunology of Infectious Disease | Pathogenic Microbiology
While T cell immunity initially limits Mycobacterium tuberculosis infection, why T cell immunity fails to sterilize the infection and allows recrudescence is not clear. One hypothesis is that T cell exhaustion impairs immunity and is detrimental to the outcome of M. tuberculosis infection. Here we provide functional evidence for the development T cell exhaustion during chronic TB. Second, we evaluate the role of the inhibitory receptor T cell immunoglobulin and mucin domain-containing-3 (TIM3) during chronic M. tuberculosis infection. We find that TIM3 expressing T cells accumulate during chronic infection, co-express other inhibitory receptors including PD1, produce less IL-2 and TNF but more IL-10, and are functionally exhausted. Finally, we show that TIM3 blockade restores T cell function and improves bacterial control, particularly in chronically infected susceptible mice. These data show that T cell immunity is suboptimal during chronic M. tuberculosis infection due to T cell exhaustion. Moreover, in chronically infected mice, treatment with anti-TIM3 mAb is an effective therapeutic strategy against tuberculosis.
DOI of Published Version
PLoS Pathog. 2016 Mar 11;12(3):e1005490. doi: 10.1371/journal.ppat.1005490. eCollection 2016. Link to article on publisher's site
Jayaraman, Pushpalatha; Jacques, Miye K.; Zhu, Chen; Steblenko, Katherine; Stowell, Britni L.; Madi, Asaf; Anderson, Ana C.; Kuchroo, Vijay K.; and Behar, Samuel M., "TIM3 Mediates T Cell Exhaustion during Mycobacterium tuberculosis Infection" (2016). Open Access Articles. 2890.
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