Biology subjects

Li, L.-X.

Publications and source records attributed to Li, L.-X..

4 recordsLinked to original sources

bioRxiv2026

CXCR6 marks polyfunctional effector CD4 T cells required for anti-Chlamydia immunity in the female reproductive tract

CD4 T cells are essential for protective immunity against Chlamydia in the female reproductive tract (FRT), yet the characteristics of protective mucosal effector CD4 T cells remain poorly defined. We previously identified the transcription factor BHLHE40 as a key regulator of polyfunctional effector CD4 T cell differentiation during Chlamydia infection. Here, we identify the chemokine receptor CXCR6 as a marker of these protective T cells. Following intravaginal Chlamydia muridarum infection, Bhlhe40-deficient mice exhibited reduced frequencies of CXCR6 CD4 T cells that correlated with impaired bacterial control. CXCR6 expression on T cells was associated with loss of stem-like features and acquisition of an effector phenotype. Compared with CXCR6- cells, CXCR6 CD4 T cells displayed enhanced proliferation and polyfunctionality by co-producing cytokines IFN-{gamma}, IL-17A, and GM-CSF. Although CXCR6 was dispensable for CD4 T cell homing to the FRT, it promoted localization to the infected epithelium and the emerging memory lymphoid clusters. Importantly, depletion of CXCR6 CD4 T cells reduced polyfunctional effectors and impaired bacterial clearance. Collectively, these findings identify CXCR6 as a marker of protective polyfunctional CD4 T cells and implicate CXCR6-dependent tissue positioning as a key component of effective mucosal immunity, highlighting CXCR6 as a potential biomarker for Chlamydia vaccine development.

immunology↗

bioRxiv2023

BHLHE40 drives protective polyfunctional CD4 T cell differentiation in the female reproductive tract against Chlamydia

The protein basic helix-loop-helix family member e40 (BHLHE40) is a transcription factor recently emerged as a key regulator of host immunity to infections, autoimmune diseases and cancer. In this study, we investigated the role of Bhlhe40 in protective T cell responses to the intracellular bacterium Chlamydia in the female reproductive tract (FRT). Mice deficient in Bhlhe40 exhibited severe defects in their ability to control Chlamydia muridarum shedding from the FRT. The heightened bacterial burdens in Bhlhe40-/-mice correlated with a marked increase in IL-10-producing T regulatory type 1 (Tr1) cells and decreased polyfunctional CD4 T cells co-producing IFN-{gamma}, IL-17A and GM-CSF. Genetic ablation of IL-10 or functional blockade of IL-10R increased CD4 T cell polyfunctionality and partially rescued the defects in bacterial control in Bhlhe40-/- mice. Using single-cell RNA sequencing coupled with TCR profiling, we detected a significant enrichment of stem-like T cell signatures in Bhlhe40-deficient CD4 T cells, whereas WT CD4 T cells were further down on the differentiation trajectory with distinct effector functions beyond IFN-{gamma} production by Th1 cells. Altogether, we identified Bhlhe40 as a key molecular driver of CD4 T cell differentiation and polyfunctional responses in the FRT against Chlamydia.

immunology↗

bioRxiv2022

IFNγ and antibody synergize to enhance protective immunity against Chlamydia dissemination and female reproductive tract reinfections

CD4 T cell-dependent IFN{gamma} production and antibody are the two best known effectors for protective immunity against Chlamydia female reproductive tract (FRT) infection. Nevertheless, mice lacking either IFN{gamma} or B cells are capable of clearing vast majority of Chlamydia from the female reproductive tract (FRT), while suffering from varying degrees of disseminated infection. In this study, we investigated whether IFN{gamma} and B cells play complimentary roles in host defense against Chlamydia and evaluated their relative contributions in systemic and mucosal tissues. Using mice deficient in both IFN{gamma} and B cells (IFN{gamma}-/- x {micro}MT), we showed that mice lacking both effectors are highly susceptible to lethal systemic Chlamydia dissemination. Passive transfer of immune convalescent serum, but not recombinant IFN{gamma}, reduced bacterial burden in both systemic and mucosal tissues in IFN{gamma}-/- x {micro}MT mice. Moreover, we observed a reduction of bacterial shedding of more than two orders of magnitude in IFN{gamma}-/- x {micro}MT mice following both Chlamydia muridarum and Chlamydia trachomatis infections. Lastly, protective immunity against C. muridarum reinfection was completely abrogated in the absence of IFN{gamma} and B cells. Our results suggest that IFN{gamma} and B cells synergize to combat bacterial dissemination, while an IFN{gamma} and B cell-independent mechanism exists for host resistance to Chlamydia in the FRT.

immunology↗

bioRxiv2020

Innate IFNγ is essential for systemic Chlamydia control while CD4 T cell-dependent IFNγ production is highly redundant in the female reproductive tract

Protective immunity to the obligate intracellular bacterium Chlamydia is thought to rely on CD4 T cell-dependent IFN{gamma} production. Nevertheless, whether IFN{gamma} is produced by other cellular source during Chlamydia infection and how CD4 T cell-dependent and -independent IFN{gamma} contribute differently to host resistance has not been carefully evaluated. In this study, we dissect the requirements of IFN{gamma} produced by innate immune cells and CD4 T cells for resolution of Chlamydia muridarum female reproductive tract (FRT) infection. After C. muridarum intravaginal inoculation, IFN{gamma}-deficient and T cell-deficient mice exhibited opposite phenotypes for survival and bacterial shedding at the FRT mucosa, demonstrating the distinct requirements for IFN{gamma} and CD4 T cells in host defense against Chlamydia. In Rag-deficient mice, IFN{gamma} produced by innate lymphocytes (ILCs) accounted for early bacterial containment and prolonged survival in the absence of adaptive immunity. Although group I ILCs are potent IFN{gamma} producers, we found that mature NK cells and ILC1 were not the sole source for innate IFN{gamma} in response to Chlamydia. T cell adoptive transfer experiments revealed that WT and IFN{gamma}-deficient CD4 T cells were equally capable of mediating effective bacterial killing in the FRT during the early stage of Chlamydia infection. Together, our results revealed that innate IFN{gamma} is essential for preventing systemic Chlamydia dissemination, whereas IFN{gamma} produced by CD4 T cells is largely dispensable at the FRT mucosa.

immunology↗