1. Enhanced survival following oral and systemic Salmonella enterica serovar Typhimurium infection in polymeric immunoglobulin receptor knockout mice
- Author
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Betz, Kristina J., Maier, Elizabeth A., Amarachintha, Surya, Wu, David, Karmele, Erik P., Kinder, Jeremy M., Steinbrecher, Kris A., McNeal, Monica M., Luzader, Deborah H., Hogan, Simon P., and Moore, Sean R.
- Subjects
Bacterial Diseases ,Physiology ,lcsh:Medicine ,Administration, Oral ,Pathology and Laboratory Medicine ,Biochemistry ,Feces ,Mice ,Salmonella ,Immune Physiology ,Medicine and Health Sciences ,Enzyme-Linked Immunoassays ,lcsh:Science ,Mice, Knockout ,Innate Immune System ,Immune System Proteins ,Receptors, Polymeric Immunoglobulin ,Salmonella enterica ,Bacterial Pathogens ,Intestines ,Survival Rate ,Infectious Diseases ,Medical Microbiology ,Salmonella Typhimurium ,Physical Sciences ,Injections, Intravenous ,Cytokines ,Pathogens ,Anatomy ,Research Article ,Colon ,Immunology ,Materials Science ,Material Properties ,Research and Analysis Methods ,Microbiology ,Permeability ,Antibodies ,Lymphatic System ,Enterobacteriaceae ,Animals ,Immunoassays ,Microbial Pathogens ,Salmonella Infections, Animal ,Bacteria ,lcsh:R ,Organisms ,Biology and Life Sciences ,Proteins ,Molecular Development ,Immunoglobulin A ,Gastrointestinal Tract ,Mice, Inbred C57BL ,Immune System ,Splenomegaly ,Immunologic Techniques ,lcsh:Q ,Lymph Nodes ,Digestive System ,Developmental Biology - Abstract
BACKGROUND:Polymeric immunoglobulin receptor (pIgR) transport of secretory immunoglobulin A (SIgA) to mucosal surfaces is thought to promote gut integrity and immunity to Salmonella enterica serovar Typhimurium (S. Typhimurium), an invasive pathogen in mice. To elucidate potential mechanisms, we assessed intestinal barrier function and both oral and systemic S. Typhimurium virulence in pIgR knockout (KO) and wildtype (WT) mice. METHODS:In uninfected animals, we harvested jejunal segments for Ussing chamber analyses of transepithelial resistance (TER); mesenteric lymph nodes (mLN) for bacterial culture; and serum and stool for IgA. Separately, we infected mice either orally or intravenously (IV) with S. Typhimurium to compare colonization, tissue dynamics, and inflammation between KOs and WTs. RESULTS:Uninfected KOs displayed decreased TER and dramatically increased serum IgA and decreased fecal IgA vs. WT; however, KO mLNs yielded fewer bacterial counts. Remarkably, WTs challenged orally with S. Typhimurium exhibited increased splenomegaly, tissue colonization, and pro-inflammatory cytokines vs. pIgR KOs, which showed increased survival following either oral or IV infection. CONCLUSIONS:Absence of pIgR compromises gut integrity but does not exacerbate bacterial translocation nor S. Typhimurium infection. These findings raise the possibility that immune adaptation to increased gut permeability and elevated serum IgA in the setting of SIgA deficiency provides compensatory protection against invasive gut pathogens.
- Published
- 2018