Clearance ofCitrobacter rodentiumRequires B Cells but Not Secretory Immunoglobulin A (IgA) or IgM Antibodies

Abstract

Citrobacter rodentium, a murine model pathogen for human enteropathogenic Escherichia coli, predominantly colonizes the lumen and mucosal surface of the colon and cecum and causes crypt hyperplasia and mucosal inflammation. Mice infected with C. rodentium develop a secretory immunoglobulin A (IgA) response, but the role of B cells or secretory antibodies in host defense is unknown. To address this question, we conducted oral C. rodentium infections in mice lacking B cells, IgA, secreted IgM, polymeric Ig receptor (pIgR), or J chain. Normal mice showed peak bacterial numbers in colon and feces at 1 week and bacterial eradication after 3 to 4 weeks. B-cell-deficient mice were equally susceptible initially but could not control infection subsequently. Tissue responses showed marked differences, as infection of normal mice was accompanied by transient crypt hyperplasia and mucosal inflammation in the colon and cecum at 2 but not 6 weeks, whereas B-cell-deficient mice had few mucosal changes at 2 weeks but severe epithelial hyperplasia with ulcerations and mucosal inflammation at 6 weeks. The functions of B cells were not mediated by secretory antibodies, since mice lacking IgA or secreted IgM or proteins required for their transport into the lumen, pIgR or J chain, cleared C. rodentium normally. Nonetheless, systemic administration of immune sera reduced bacterial numbers significantly in normal and pIgR-deficient mice, and depletion of IgG abrogated this effect. These results indicate that host defense against C. rodentium depends on B cells and IgG antibodies but does not require production or transepithelial transport of IgA or secreted IgM.

Identification and characterization of Cri1, a locus controlling mortality during Citrobacter rodentium infection in mice

“…28 Although the Il7r gene seems relatively far proximal of the peak linkage region of the Cri1 locus, it is an intriguing candidate as B-cell function has been found to be essential for C. rodentium infection survival. 19,29,30 Ultimately, however, a continued systematic genetic approach may be required to identify the gene underlying the Cri1 locus. For that purpose, we are currently generating subcongenic mice that transfer smaller portions of the Cri1 locus from the B6 parental strain onto the C3Ou genetic background.…”

Fcγ Receptor Regulation of Citrobacter rodentium Infection

“…The susceptibility to C. rodentium infection in FcR␥ Ϫ/Ϫ mice is thus explained by a broad decrease in the efficacy of the immune response associated with defense against this mucosal pathogen. Moreover, the effects (3,9,17). We examined the uptake of bacterium-IgG complexes in various Fc␥R-deficient DCs.…”

“…C. rodentium is usually spontaneously eradicated by day 28 after oral administration in wild-type mice (10). From the infection experiments using immune cell-deficient mice, CD4 ϩ T cells, B cells, and IgG, but not secretory IgA or IgM, have been shown to play a critical role in eradicating this pathogen (3,9,17). It is speculated that C. rodentium-specific IgGs produced by B cells after stimulation of CD4 ϩ T cells are necessary to eradicate this pathogen.…”

Cathelicidin Mediates Innate Intestinal Defense against Colonization with Epithelial Adherent Bacterial Pathogens

“…colon and Ͻ10 colonies per organ in spleen and mesenteric lymph nodes. Identity of representative bacterial colonies was verified by PCR (21).…”

“…The following bacteria were used: C. rodentium (21) To determine total bacterial numbers in the colon and feces of Cnlp…”