Rotavirus is a major cause of pediatric diarrheal illness worldwide. To explore the role of organized intestinal lymphoid tissues in
infection by and immunity to rotavirus,
lymphotoxin alpha-deficient (LTα(-/-)) mice that lack Peyer's patches and mesenteric lymph nodes were orally infected with murine rotavirus. Systemic rotavirus was cleared within 10 days in both LTα(-/-) and wild-type mice, and both strains developed early and sustained serum antirotavirus antibody responses. However, unlike wild-type mice, which resolved the intestinal
infection within 10 days, LTα(-/-) mice shed fecal virus for approximately 50 days after inoculation. The resolution of fecal virus shedding occurred concurrently with induction of intestinal rotavirus-specific
IgA in both mouse strains. Induction of intestinal rotavirus-specific
IgA in LTα(-/-) mice correlated with the (late) appearance of
IgA-producing plasma cells in the small intestine. This, together with the absence of rotavirus-specific serum
IgA, implies that secretory rotavirus-specific
IgA was produced locally. These findings indicate that serum
IgG responses are insufficient and imply that local intestinal
IgA responses are important for the clearance of rotavirus from intestinal tissues. Furthermore, they show that while LTα-dependent lymphoid tissues are important for the generation of
IgA-producing B cells in the intestine, they are not absolutely required in the setting of
rotavirus infection. Moreover, the induction of local
IgA-producing B cell responses can occur late after
infection and in an LTα-independent manner.