I have to introduce this paper for Wednesday's paper discussion, "Prenatal maternal infection promotes tissue-specific immunity and inflammation in offspring." Need to know it perfectly and be able to put together an intro presentation. Here is the overview page of the article, "INTRODUCTION: One fundamental property of the immune system is its ability to develop memory of previous encounters, resulting in enhanced responsiveness to subsequent challenges. This phenomenon includes not only the adaptive immune system but also innate cells and tissue stem cells. The con- cept of host imprinting by infection leading to altered responses to subsequent challenge is of particular interest in the context of pregnancy, which represents a fundamental developmen- tal window for the immune system. RATIONALE: Most infections encountered by mammals, including those experienced during pregnancy, are mild and transient. How these infections shape offspring tissue immunity and tissue predisposition to inflammatory disorders in the long term remains to be addressed. RESULTS: Infection of timed-pregnant dams (day 10.5) with an attenuated strain of the food- borne pathogen Yersinia pseudotuberculosis (yopM) was transient and maternally restricted. Adult offspring of previously infected dams harbored a higher number of T helper 17 (TH17) cells but no other cell subsets in the small and large intestinal lamina propria. No changes were observed at other barrier tissues. Trans- fer of transgenic T cells specific for a commen- sal antigen revealed that maternal infection affected the offspring intestinal milieu in a manner that enhanced T H 17 cell reactivity toward the microbiota. Cross-fostering exper- iments demonstrated that the increased TH17 cells resulting from maternal infection was im- printed in utero. Among various inflammatory mediators, the cytokine interleukin-6 (IL-6) was significantly increased in the serum of dams infected with yopM. Injection of IL-6 alone to pregnant dams significantly increased TH17 cell numbers within the guts of offspring. Conversely, blockade of IL-6 in infected dams prevented this increase in offspring. Further- more, injection of IL-6 to germ-free pregnant dams and conventionalization of their off- spring after weaning revealed that prenatal establishment and postnatal maintenance of IL-6–mediated tissue imprinting are indepen- dent of the maternal microbiota but allow the offspring to mount enhanced T H 17 cell responses to postnatal microbiota exposure. IL6RA was expressed in all fetal intestinal epithelial cells, and specific deletion of IL6RA from epithelial cells significantly reduced Th17 responses within the gut of offspring from IL-6–exposed dams. Using complementary approaches, including assay for transposase- accessible chromatin with high-throughput sequencing (ATAC-seq) and single-cell RNA sequencing, we found that increased IL-6 during pregnancy had immediate effects (on fetal cells) and long-term effects (in the adu
I have to introduce this paper for Wednesday's paper discussion, "Prenatal maternal infection promotes tissue-specific immunity and inflammation in offspring." Need to know it perfectly and be able to put together an intro presentation. Here is the overview page of the article, "INTRODUCTION: One fundamental property of the immune system is its ability to develop memory of previous encounters, resulting in enhanced responsiveness to subsequent challenges. This phenomenon includes not only the adaptive immune system but also innate cells and tissue stem cells. The con- cept of host imprinting by infection leading to altered responses to subsequent challenge is of particular interest in the context of pregnancy, which represents a fundamental developmen- tal window for the immune system. RATIONALE: Most infections encountered by mammals, including those experienced during pregnancy, are mild and transient. How these infections shape offspring tissue immunity and tissue predisposition to inflammatory disorders in the long term remains to be addressed. RESULTS: Infection of timed-pregnant dams (day 10.5) with an attenuated strain of the food- borne pathogen Yersinia pseudotuberculosis (yopM) was transient and maternally restricted. Adult offspring of previously infected dams harbored a higher number of T helper 17 (TH17) cells but no other cell subsets in the small and large intestinal lamina propria. No changes were observed at other barrier tissues. Trans- fer of transgenic T cells specific for a commen- sal antigen revealed that maternal infection affected the offspring intestinal milieu in a manner that enhanced T H 17 cell reactivity toward the microbiota. Cross-fostering exper- iments demonstrated that the increased TH17 cells resulting from maternal infection was im- printed in utero. Among various inflammatory mediators, the cytokine interleukin-6 (IL-6) was significantly increased in the serum of dams infected with yopM. Injection of IL-6 alone to pregnant dams significantly increased TH17 cell numbers within the guts of offspring. Conversely, blockade of IL-6 in infected dams prevented this increase in offspring. Further- more, injection of IL-6 to germ-free pregnant dams and conventionalization of their off- spring after weaning revealed that prenatal establishment and postnatal maintenance of IL-6–mediated tissue imprinting are indepen- dent of the maternal microbiota but allow the offspring to mount enhanced T H 17 cell responses to postnatal microbiota exposure. IL6RA was expressed in all fetal intestinal epithelial cells, and specific deletion of IL6RA from epithelial cells significantly reduced Th17 responses within the gut of offspring from IL-6–exposed dams. Using complementary approaches, including assay for transposase- accessible chromatin with high-throughput sequencing (ATAC-seq) and single-cell RNA sequencing, we found that increased IL-6 during pregnancy had immediate effects (on fetal cells) and long-term effects (in the adu
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Prenatal infections play a crucial role in shaping immune responses, with immune memory beginning before birth. This period serves as an imprinting window, raising questions about lasting tissue-specific effects. A study on Yersinia infection highlights maternal-restricted impacts, showing a gut-specific increase in offspring TH17 cells linked by IL-6 to fetal epithelium. Mechanistically, in utero imprinting has lasting effects into adulthood, as evidenced by ATAC-seq and scRNA-seq findings,...