Clearance of Citrobacter rodentium requires B cells but not secretory immunoglobulin A (IgA) or IgM antibodies.
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.
Maaser
Christian
C
Department of Medicine, University of California, San Diego, La Jolla, California 92093, USA.
Housley
Michael P
MP
Iimura
Mitsutoshi
M
Smith
Jennifer R
JR
Vallance
Bruce A
BA
Finlay
B Brett
BB
Schreiber
John R
JR
Varki
Nissi M
NM
Kagnoff
Martin F
MF
Eckmann
Lars
L
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002432:Cecum / Q000276:immunology / Q000382:microbiology; D044082:Citrobacter rodentium / Q000472:pathogenicity*; D003106:Colon / Q000276:immunology / Q000382:microbiology; D004756:Enterobacteriaceae Infections / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D007071:Immunoglobulin A, Secretory / Q000096:biosynthesis* / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G; D007075:Immunoglobulin M