Tissue resident memory T cell responses in primary and secondary lung infection to Chlamydia muridarum
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Date
2020
Authors
Rashu, Md Rasheduzzaman
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Abstract
Chlamydia is an obligate intracellular bacterium that causes ectopic pregnancy, infertility, trachoma, and pneumonia. It causes 90-92 million cases of chlamydial infection globally each year. Although great effort has been made, there is no vaccine to prevent human chlamydial diseases. One of the major reasons is the lack of a clear understanding of the exact mechanism of long-lasting protection in chlamydial infections. The previous studies have shown that cell-mediated immunity particularly IFNγ producing T cells are the major cell type related to protection. However, the pattern of memory T cell responses especially the resident memory T cells (Trm) in chlamydial infection remains unclear. The major goal of this study is to explore the nature of memory T cell response in chlamydial infection. Chlamydia muridarum is a mice specific model organism vastly used to elucidate the immunobiology of chlamydia. Using the female Balb/c mouse model, we show here that intranasal infection with C. muridarum induces effector memory T (Tem) cells, increase after primary infection and produce cytokines IFNγ and TNFα in the lung. However, central memory T cells (Tcm cells) decrease proportionally over time with the progression of the infection. More importantly, we found significant Trm cell responses in the lung, which persist for a long time after the clearance of the pathogen. Both CD8+and CD4+ Trm cells were identified. Notably, higher level and longer persistence of CD8+ Trm cells were observed compared to CD4+ Trm cells. Cytokine profiling showed that the Trm cells produce IFNγ, TNFα, and IL-2 even a long time after the resolution of the infection. To test the responses of the Trm in secondary infection, we challenged mice with the same dose of C. muridarum and examined their Trm responses in correlation with the pattern of disease course in a primary and secondary infection. We found that IFNγ, TNFα, and IL-2 production by Trm cells were significantly higher than those of Trm cells in primary infection, suggesting a better
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protection by Trm cells in the secondary infection. Indeed, these secondary infections are associated with significantly less body-weight loss, less lung associated pathology with an undetectable number of bacteria in the lung. These results support the notion that chlamydia infection can induce significant Trm cells, which may play an important protective role in C. muridarum mediated lung infection.
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Keywords
Chlamydia, Tissue resident T cells, Lung, cytokine