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Characterizing Early T Cell Responses in Nonhuman Primate Model of Tuberculosis

Tuberculosis (TB), caused by , remains a leading infectious disease killer worldwide with 1.4 million TB deaths in 2019. While the majority of infected population maintain an active control of the bacteria, a subset develops active disease leading to mortality. Effective T cell responses are critica...

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Bibliographic Details
Published in:Frontiers in immunology 2021-08, Vol.12, p.706723-706723
Main Authors: Sharan, Riti, Singh, Dhiraj Kumar, Rengarajan, Jyothi, Kaushal, Deepak
Format: Article
Language:English
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Summary:Tuberculosis (TB), caused by , remains a leading infectious disease killer worldwide with 1.4 million TB deaths in 2019. While the majority of infected population maintain an active control of the bacteria, a subset develops active disease leading to mortality. Effective T cell responses are critical to TB immunity with CD4 and CD8 T cells being key players of defense. These early cellular responses to TB infection have not yet been studied in-depth in either humans or preclinical animal models. Characterizing early T cell responses in a physiologically relevant preclinical model can provide valuable understanding of the factors that control disease development. We studied -specific T cell responses in the lung compartment of rhesus macaques infected with either a low- or a high-dose of CDC1551 aerosol. Relative to baseline, significantly higher -specific CD4 IFN-γ and TNF- T cell responses were observed in the BAL of low dose infected macaques as early as week 1 post TB infection. The IFN-γ and TNF- response was delayed to week 3 post infection in -specific CD4 and CD8 T cells in the high dose group. The manifestation of earlier T cell responses in the group exposed to the lower dose suggested a critical role of these cytokines in the antimycobacterial immune cascade, and specifically in the granuloma formation to contain the bacteria. However, a similar increase was not reflected in the CD4 and CD8 IL-17 T cells at week 1 post infection in the low dose group. This could be attributed to either a suppression of the IL-17 response or a lack of induction at this early stage of infection. On the contrary, there was a significantly higher IL-17 response in -specific CD4 and CD8 T cells at week 3 in the high dose group. The results clearly demonstrate an early differentiation in the immunity following low dose and high dose infection, largely represented by differences in the IFN-γ and TNF-α response by -specific T cells in the BAL. This early response to antigen expression by the bacteria could be critical for both bacterial growth control and bacterial containment.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2021.706723