scholarly journals Circulating immunity protects the female reproductive tract from Chlamydia infection

2021 ◽  
Vol 118 (21) ◽  
pp. e2104407118
Author(s):  
Jasmine C. Labuda ◽  
Oanh H. Pham ◽  
Claire E. Depew ◽  
Kevin D. Fong ◽  
Bokyung S. Lee ◽  
...  
Keyword(s):  
T Cells ◽  
Cd4 T Cells ◽  
Reproductive Tract ◽  
Vaccine Development ◽  
Female Reproductive Tract ◽  
Chlamydia Infection ◽  
Immune Memory ◽  
Memory Cd4 T Cells ◽  
Barrier Tissues ◽  
Memory Lymphocytes

Anatomical positioning of memory lymphocytes within barrier tissues accelerates secondary immune responses and is thought to be essential for protection at mucosal surfaces. However, it remains unclear whether resident memory in the female reproductive tract (FRT) is required for Chlamydial immunity. Here, we describe efficient generation of tissue-resident memory CD4 T cells and memory lymphocyte clusters within the FRT after vaginal infection with Chlamydia. Despite robust establishment of localized memory lymphocytes within the FRT, naïve mice surgically joined to immune mice, or mice with only circulating immunity following intranasal immunization, were fully capable of resisting Chlamydia infection via the vaginal route. Blocking the rapid mobilization of circulating memory CD4 T cells to the FRT inhibited this protective response. These data demonstrate that secondary protection in the FRT can occur in the complete absence of tissue-resident immune cells. The ability to confer robust protection to barrier tissues via circulating immune memory provides an unexpected opportunity for vaccine development against infections of the FRT.

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

2020 ◽  
Author(s):  
Miguel A.B. Mercado ◽  
Wuying Du ◽  
Priyangi A. Malaviarachchi ◽  
Jessica I. Gann ◽  
Lin-Xi Li
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Reproductive Tract ◽  
Early Stage ◽  
Female Reproductive Tract ◽  
Cd4 T Cell ◽  
Bacterial Killing ◽  
Group I ◽  
Deficient Mice

AbstractProtective immunity to the obligate intracellular bacterium Chlamydia is thought to rely on CD4 T cell-dependent IFNγ production. Nevertheless, whether IFNγ is produced by other cellular source during Chlamydia infection and how CD4 T cell-dependent and -independent IFNγ contribute differently to host resistance has not been carefully evaluated. In this study, we dissect the requirements of IFNγ produced by innate immune cells and CD4 T cells for resolution of Chlamydia muridarum female reproductive tract (FRT) infection. After C. muridarum intravaginal inoculation, IFNγ-deficient and T cell-deficient mice exhibited opposite phenotypes for survival and bacterial shedding at the FRT mucosa, demonstrating the distinct requirements for IFNγ and CD4 T cells in host defense against Chlamydia. In Rag-deficient mice, IFNγ 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 IFNγ producers, we found that mature NK cells and ILC1 were not the sole source for innate IFNγ in response to Chlamydia. T cell adoptive transfer experiments revealed that WT and IFNγ-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 IFNγ is essential for preventing systemic Chlamydia dissemination, whereas IFNγ produced by CD4 T cells is largely dispensable at the FRT mucosa.

scholarly journals Inactivated virus vaccine BBV152/Covaxin elicits robust cellular immune memory to SARS-CoV-2 and variants of concern

2021 ◽  
Author(s):  
Rajesh Vikkurthi ◽  
Asgar Ansari ◽  
Anupama R Pai ◽  
Someshwar Nath Jha ◽  
Shilpa Sachan ◽  
...  
Keyword(s):  
T Cells ◽  
Virus Vaccine ◽  
Cd4 T Cells ◽  
Vaccine Development ◽  
Natural Infection ◽  
Immune Memory ◽  
Booster Immunization ◽  
Tfh Cells ◽  
Fold Reduction ◽  
Cellular Immune

The characteristics of immune memory established in response to inactivated SARS-CoV-2 vaccines remains unclear. We determined the magnitude, quality and persistence of cellular and humoral memory responses up to 6 months after vaccination with BBV152/Covaxin. Here, we show that the quantity of vaccine-induced spike- and nucleoprotein-antibodies is comparable to that following natural infection and the antibodies are detectable up to 6 months. The RBD-specific antibodies decline in the range of 3 to 10-fold against the SARS-CoV-2 variants in the order of alpha (B.1.1.7) > delta (B.1.617.2) > beta (B.1.351), with no observed impact of gamma (P.1) and kappa (B.1.617.1) variant. We found that the vaccine induces memory B cells, similar to natural infection, which are impacted by virus variants in the same order as antibodies. The vaccine further induced antigen-specific functionally potent multi-cytokine expressing CD4+ T cells in ~85% of the subjects, targeting spike and nucleoprotein of SARS-CoV-2. Marginal ~1.3 fold-reduction was observed in vaccine-induced CD4+ T cells against the beta variant, with no significant impact of the alpha and the delta variants. The antigen-specific CD4+ T cells were populated in the central memory compartment and persisted up to 6 months of vaccination. Importantly the vaccine generated Tfh cells that are endowed with B cell help potential, similar to the Tfh cells induced after natural infection. Altogether, these findings establish that the inactivated virus vaccine BBV152 induces robust immune memory to SARS-CoV-2 and variants of concern, which persist for at least 6 months after vaccination. This study provides insight into the attributes of BBV152-elicited immune memory, and has implication for future vaccine development, guidance for use of inactivated virus vaccine, and booster immunization.

scholarly journals Stem-Cell-like Qualities of Immune Memory; CD4+ T Cells Join the Party

2012 ◽  
Vol 10 (2) ◽  
pp. 107-108 ◽  
Author(s):  
C. John Luckey ◽  
Casey T. Weaver
Keyword(s):  
T Cells ◽  
Stem Cell ◽  
Cd4 T Cells ◽  
Immune Memory ◽  
Memory Cd4 T Cells

scholarly journals HIV efficiently infects T cells from the endometrium and remodels them to promote systemic viral spread

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Tongcui Ma ◽  
Xiaoyu Luo ◽  
Ashley F George ◽  
Gourab Mukherjee ◽  
Nandini Sen ◽  
...  
Keyword(s):  
T Cells ◽  
Reproductive Tract ◽  
Hiv Transmission ◽  
Nearest Neighbor ◽  
Female Reproductive Tract ◽  
Receptor Expression ◽  
Endometrial Cells ◽  
Viral Spread ◽  
Cell Remodeling ◽  
Memory Cd4 T Cells

The female reproductive tract (FRT) is the most common site of infection during HIV transmission to women, but viral remodeling complicates characterization of cells targeted for infection. Here, we report extensive phenotypic analyses of HIV-infected endometrial cells by CyTOF, and use a ‘nearest neighbor’ bioinformatics approach to trace cells to their original pre-infection phenotypes. Like in blood, HIV preferentially targets memory CD4+ T cells in the endometrium, but these cells exhibit unique phenotypes and sustain much higher levels of infection. Genital cell remodeling by HIV includes downregulating TCR complex components and modulating chemokine receptor expression to promote dissemination of infected cells to lymphoid follicles. HIV also upregulates the anti-apoptotic protein BIRC5, which when blocked promotes death of infected endometrial cells. These results suggest that HIV remodels genital T cells to prolong viability and promote viral dissemination and that interfering with these processes might reduce the likelihood of systemic viral spread.

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

2020 ◽  
Author(s):  
Miguel A.B. Mercado ◽  
Wuying Du ◽  
Priyangi A. Malaviarachchi ◽  
Jessica I. Gann ◽  
Lin-Xi Li
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd4 T Cells ◽  
Reproductive Tract ◽  
Female Reproductive Tract ◽  
Cd4 T Cell ◽  
Type I ◽  
Bacterial Killing ◽  
Chlamydia Muridarum ◽  
Deficient Mice

Protective immunity against the obligate intracellular bacterium Chlamydia has long been thought to rely on CD4 T cell-dependent IFNγ production. Nevertheless, whether IFNγ is produced by other cellular sources during Chlamydia infection and how CD4 T cell-dependent and -independent IFNγ contribute differently to host resistance has not been carefully evaluated. In this study, we dissect the requirements of IFNγ produced by innate immune cells and CD4 T cells for resolution of Chlamydia muridarum female reproductive tract (FRT) infection. After C. muridarum intravaginal infection, IFNγ-deficient and T cell-deficient mice exhibited opposite phenotypes for survival and bacterial shedding at the FRT mucosa, demonstrating the distinct requirements for IFNγ and CD4 T cells in host defense against Chlamydia. In Rag1-deficient mice, IFNγ produced by innate lymphocytes (ILCs) accounted for early bacterial control and prolonged survival in the absence of adaptive immunity. Although type I ILCs are potent IFNγ producers, we found that mature NK cells and ILC1s were not the sole source for innate IFNγ in response to Chlamydia. By conducting T cell adoptive transfer, we showed definitively that IFNγ-deficient CD4 T cells were sufficient for effective bacterial killing in the FRT during the first 21 days of infection and reduced bacterial burden more than 1,000-fold, albeit mice receiving IFNγ-deficient CD4 T cells failed to completely eradicate the bacteria from the FRT like their counterparts receiving WT CD4 T cells. Together, our results revealed that innate IFNγ is essential for preventing systemic Chlamydia dissemination, whereas IFNγ produced by CD4 T cells is largely redundant at the FRT mucosa.

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