Summary null null Lymphangitis and the formation of tertiary lymphoid organs (TLOs) in the mesentery are features of Crohn’s disease. Here, we examined the genesis of these TLOs and their impact on disease progression. Whole-mount and intravital imaging of the ileum and ileum-draining collecting lymphatic vessels (CLVs) draining to mesenteric lymph nodes from TNFΔARE mice, a model of ileitis, revealed TLO formation at valves of CLVs. TLOs obstructed cellular and molecular outflow from the gut an...
#1Sven Kratochvil(MIT: Massachusetts Institute of Technology)H-Index: 6
#2Chen-Hsiang Shen(NIH: National Institutes of Health)H-Index: 18
Last. Facundo D. Batista(MIT: Massachusetts Institute of Technology)H-Index: 56
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Repeat antigens, such as the Plasmodium falciparum circumsporozoite protein (PfCSP), use both sequence degeneracy and structural diversity to evade the immune response. A few PfCSP-directed antibodies have been identified that are effective at preventing malaria infection, including CIS43, but how these repeat-targeting antibodies might be improved has been unclear. Here, we engineered a humanized mouse model in which B cells expressed inferred human germline CIS43 (iGL-CIS43) B cell receptors a...
#1D. Hoffman(Weizmann Institute of Science)H-Index: 1
#2Y. Tevet(Weizmann Institute of Science)H-Index: 1
Last. Roi Avraham(Weizmann Institute of Science)H-Index: 22
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Interactions between intracellular bacteria and mononuclear phagocytes give rise to diverse cellular phenotypes that may determine the outcome of infection. Recent advances in single-cell RNA sequencing (scRNA-seq) have identified multiple subsets within the mononuclear population, but implications to their function during infection are limited. Here, we surveyed the mononuclear niche of intracellular Salmonella Typhimurium (S.Tm) during early systemic infection in mice. We described eclipse-lik...
Last. Kelvin P. Lee(Roswell Park Cancer Institute)H-Index: 33
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Humoral immunity is essential for protection against pathogens, emphasized by the prevention of 2-3 million deaths worldwide annually by childhood immunizations. Long-term protective immunity is dependent on the continual production of neutralizing antibodies by the subset of long-lived plasma cells (LLPCs). LLPCs are not intrinsically long-lived, but require interaction with LLPC niche stromal cells for survival. However, it remains unclear which and how these interactions sustain LLPC survival...
#1Ayaka Sugiura(VUMC: Vanderbilt University Medical Center)H-Index: 6
#2Gabriela Andrejeva(VUMC: Vanderbilt University Medical Center)H-Index: 10
Last. Jeffrey C. Rathmell(VUMC: Vanderbilt University Medical Center)H-Index: 80
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Summary null null Antigenic stimulation promotes T cell metabolic reprogramming to meet increased biosynthetic, bioenergetic, and signaling demands. We show that the one-carbon (1C) metabolism enzyme methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) regulates de novo purine synthesis and signaling in activated T cells to promote proliferation and inflammatory cytokine production. In pathogenic T helper-17 (Th17) cells, MTHFD2 prevented aberrant upregulation of the transcription factor FoxP3 alo...
Retinol is shuttled to myeloid cells for conversion to retinoic acid, but the receptor facilitating uptake of SAA:retinol complexes on myeloid cells is unknown. In a recent issue of Science, Bang et al. (2021) use genetic and biochemical approaches to reveal this critical receptor to be LRP1 and show that this axis is essential for intestinal innate and adaptive immune responses.
#1Junnan Wu(UPenn: University of Pennsylvania)H-Index: 4
#2Ziyuan Ma(UPenn: University of Pennsylvania)H-Index: 4
Last. Thomas G. Dunn(UPenn: University of Pennsylvania)H-Index: 9
view all 18 authors...
The incidence and severity of sepsis is higher among individuals of African versus European ancestry. We found that genetic risk variants (RVs) in the trypanolytic factor apolipoprotein L1 (APOL1), present only in individuals of African ancestry, were associated with increased sepsis incidence and severity. Serum APOL1 levels correlated with sepsis and COVID-19 severity, and single-cell sequencing in human kidneys revealed high expression of APOL1 in endothelial cells. Analysis of mice with endo...
Last. Guadalupe Sabio(Centro Nacional de Investigaciones Cardiovasculares)H-Index: 29
view all 12 authors...
Summary null null Peritoneal immune cells reside unanchored within the peritoneal fluid in homeostasis. Here, we examined the mechanisms that control bacterial infection in the peritoneum using a mouse model of abdominal sepsis following intraperitoneal Escherichia coli infection. Whole-mount immunofluorescence and confocal microscopy of the peritoneal wall and omentum revealed that large peritoneal macrophages (LPMs) rapidly cleared bacteria and adhered to the mesothelium, forming multilayered ...
#1Travis E. Faust(UMMS: University of Massachusetts Medical School)H-Index: 1
#2Dorothy P. Schafer(UMMS: University of Massachusetts Medical School)H-Index: 22
Maternal infection during pregnancy increases the offspring's risk of developing neurodevelopmental disorders. While IL-6 is involved, the mechanism by which IL-6 and other cytokines affect developing neural circuits is unknown. In this issue of Immunity, Mirabella et al. (2021) show that the pro-inflammatory cytokine IL-6 specifically increases synaptogenesis in immature excitatory neurons through downstream neuronal STAT3-dependent transcriptional regulation of Rgs4.
#2Jisun Jung(WashU: Washington University in St. Louis)
Last. Devesha H. Kulkarni(WashU: Washington University in St. Louis)H-Index: 9
view all 20 authors...
Summary null null Cryptosporidium can cause severe diarrhea and morbidity, but many infections are asymptomatic. Here, we studied the immune response to a commensal strain of Cryptosporidium tyzzeri (Ct-STL) serendipitously discovered when conventional type 1 dendritic cell (cDC1)-deficient mice developed cryptosporidiosis. Ct-STL was vertically transmitted without negative health effects in wild-type mice. Yet, Ct-STL provoked profound changes in the intestinal immune system, including inductio...
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