Reovirus type 1 Lang: A model to study M cell specific pathogen interactions and secretory IgA function in the intestine

Reovirus type 1 Lang (T1L), a non-enveloped, 85 nm diameter mouse pathogen, adheres selectively to M cells and exploits M cell transport to gain access to the intestinal mucosa. M cell adherence requires proteolytic conversion in the intestine to an intermediate subviral particle (ISVP) that has lost the outer capsid protein, σ3, cleaved the capsid protein, μ1c, and extended the viral adhesin, σ1. The M cell surface component(s) exploited by reovirus are not known. Using a microbial overlay assay on rabbit Peyer's patch paraffin sections, I have demonstrated that T1L binding to M cells involves a glycoprotein displaying the carbohydrate structure NeuAc α(2-3)Gal/GalNAc recognized by the lectin MAL II. This structure is present on all intestinal epithelial cells but appears to be more accessible to virus-sized particles on M cells and the follicle-associated epthelium (FAE).;T1L infection of the Peyer's patches evokes cellular and humoral immune responses that include secretory IgA (SIgA) and serum IgG as well as specific CTLs. Adult mice clear reovirus from the mucosa within ten days. It is not known which immune effector is most important in protection against viral entry on re-challenge. For other enteric pathogens, SIgA protects against mucosal re-infection by preventing epithelial adherence. However, IgA as well as IgA/antigen complexes bind to apical surfaces of M cells; IgG does not. Thus, reovirus-specific IgA may facilitate reovirus entry via M cells rather than protect.;I have examined the effects of orally-administered reovirus-specific IgA and IgG monoclonal antibodies (MAbs) on T1L entry and local immune responses in Peyer's patches. Anti-σ3 and μ1c IgA and IgG MAbs did not prevent viral entry or local immune responses. Anti-σ1 IgA MAbs were not available. Oral administration of reovirus in adult wild-type mice resulted in reovirus-specific IgA in feces and IgG in serum, including antibodies against σ1. IgA knockout mice had high levels of serum IgG and detectable serum IgM. When wild-type and knockout mice were re-challenged 21 days after initial exposure Peyer's patches from wild-type mice were virus-free whereas IgA knockout mice were infected. This demonstrates that IgA plays a crucial role in preventing reovirus entry into Peyer's patch mucosa.