Chlamydia muridarum Causes Persistent Subclinical Infection and Elicits Innate and Adaptive Immune Responses in C57BL/6J, BALB/cJ, and J:ARC(S) Mice Following Exposure to Shedding Mice.

Noah Mishkin, Sebastian E Carrasco, Michael Palillo, Panagiota Momtsios, Cheryl Woods, Kenneth S Henderson, Ana Leda F Longhini, Chelsea Otis, Rui Gardner, Ann M Joseph, Gregory F Sonnenberg, Jack Palillo, Rodolfo J Ricart Arbona, Neil S Lipman
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Abstract

Chlamydia muridarum (Cm) has reemerged as a moderately prevalent infectious agent in research mouse colonies. Despite its experimental use, few studies evaluate Cm's effects on immunocompetent mice following its natural route of infection. A Cm field isolate was administered (orogastric gavage) to 8-wk-old female BALB/cJ (C) mice. After shedding was confirmed (through 95 d), these mice were cohoused with naïve C57BL/6J (B6), C, and Swiss (J:ARC[S]) mice (n = 28/strain) for 30 d. Cohoused mice (n = 3 to 6 exposed and 1 to 6 control/strain) were evaluated 7, 14, 21, 63, 120, and 180 d post-cohousing (DPC) via hemograms, serum biochemistry analysis, fecal quantitative PCR, histopathology, and Cm major outer membrane protein immunohistochemistry. Immunophenotyping was performed on spleen (B6, C, and S; n = 6/strain) and intestines (B6; n = 6) at 14 and 63 DPC. Serum cytokine concentrations were measured (B6; n = 6 exposed and 2 control) at 14 and 63 DPC. All B6 mice were shedding Cm by 3 through 180 DPI. One of 3 C and 1 of 6 S mice began shedding Cm at 3 and 14 DPC, respectively, with the remaining shedding thereafter. Clinical pathology was nonremarkable. Minimal-to-moderate enterotyphlocolitis and gastrointestinal-associated lymphoid tissue (GALT) hyperplasia were observed in 15 and 47 of 76 Cm-infected mice, respectively. Cm antigen was frequently detected in GALT-associated surface intestinal epithelial cells. Splenic immunophenotyping revealed increased monocytes and shifts in T-cell population subsets in all strains/time points. Gastrointestinal immunophenotyping (B6) revealed sustained increases in total inflammatory cells and elevated cytokine expression in innate lymphoid and effector T cells (large intestine). Elevated concentrations of proinflammatory cytokines were detected in the serum (B6). Results demonstrate that while clinical disease was not appreciated, 3 commonly used strains of mice are susceptible to chronic enteric Cm infection which may alter various immune responses. Considering the widespread use of mice to model gastrointestinal disease, institutions should consider excluding Cm from their colonies.

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AALAS Journal Updates for Authors. Chlamydia muridarum Causes Persistent Subclinical Infection and Elicits Innate and Adaptive Immune Responses in C57BL/6J, BALB/cJ, and J:ARC(S) Mice Following Exposure to Shedding Mice. The Final Scene. Investigating the Effect of Enterally Administered Capromorelin on Body Weight in Mice (Mus musculus). Comparison of Terminal Elbow Extension between Humans and Baboons (Papio anubis).
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