ELSEVIER Veterinary Immunology and Immunopathology 54(1996) 163-169 Veterinary immunology and immunopathokgy Mucosal immunity: an overview and studies of enteric and respiratory coronavirus infections in a swine model of enteric disease Linda J. Saif Food Animd Health Research Progrum, Department of Veterinary Preventive Medicine. Ohio Agricultural Reseurch und Development Center, The Ohio Stute University, Wooster, OH 44691. USA Abstract Based on the tenet of a common mucosal immune system, antigenic stimulation at one mucosal site results in the distribution of antigen-specific IgA precursor cells to distant mucosal sites. However, recent studies suggest that functional compartmentalization and limited reciprocity may exist within some components of the common mucosal immune system. Although oral immuniza- tion is often very effective in inducing immunity to respiratory pathogens, the converse (respira- tory immunization to prevent enteric diseases) may not be as effective. To address this question and to study interactions between the bronchus-associated (BALT) and gut-associated (GALT) lymphoid tissues related to protective immunity, we used as a model two antigenically related porcine coronaviruses which replicate primarily in the intestine (transmissible gastroenteritis virus, TGEV) or respiratory tract (porcine respiratory coronavirus, PRCV). The tissue distribution and magnitude of the antibody secreting cell (ASC) responses (measured by ELISPOT) and cell-medi- ated immune responses (measured by lymphoproliferative assays, LPA) coincided with the viral tissue tropisms. Immunization via GALT (gut infection with TGEV) elicited high numbers of IgA ASC and high LPA responses in GALT (gut lamina propria, LP or mesenteric lymph nodes, MLN), but lower responses in BALT (bronchial lymph nodes, BLN) and induced complete protection against enteric TGEV challenge. In contrast immunization via BALT (respiratory infection with PRCV) elicited systemic type responses (high numbers of IgG ASC in the BLN), but few ASC and low LPA responses in the gut LP or MLN and induced only partial protection against enteric TGEV challenge. Thus administration of vaccines intranasally may not be optimally effective for inducing intestinal immunity in contrast to the reported efficacy of oral vaccines for inducing respiratory immunity. 0165-2427/96/$1.5.00 Published by Elsevier Science B.V. PII SO1 65.2427(96)05702-9 1. The Mucosal Immune System A unique mucosal immune system independent of the systemic immune system has evolved to protect mucosal surfaces from pathogens and to exclude environmental antigens and foreign proteins thereby preventing them from evoking systemic-type inflammatory immune responses (Reviewed in Newby. 1984; Mestecky, 1987; Brandtzaeg, 1992: McGhee et al. 1992: Husband, 1993). The mucosal immune system is characterized by a preponderance of secretory (S) IgA antibodies selectively secreted onto mucosal surfaces by an active transport mechanism (polyimmunoglobulin receptor, PIgR). The SIgA antibodies play a major role in preservation of mucosal integrity by down-regulation of systemic type immune responses, preventing invasion of pathogens from the mucosa by blocking of attachment or invasion, neutralization (in the lumen or intracellularly) and immune exclusion. These functions are in contrast to systemically induced IgG antibodies which mediate inflammatory reactions leading to the killing and elimination of pathogens, thereby maintaining the sterility of systemic organs and tissues. Although in earlier studies, SIgA was envisioned to act mainly at the luminal mucosal surfaces. recent data suggest that dimeric IgA may bind antigens on the basolateral side of intestinal epithelial cells (Kaetzel et al., 1992). These immune complexes would then be transported across the epithelial cell via the PIgR and secreted back into the intestinal lumen thereby eliminating foreign antigens that have penetrated through the epithelium. At least two other recent reports have suggested that SIgA may function intracellularly in host defense by the inhibition of viral replication or assembly in vitro (Armstrong and Dimmock, 1992; Marzanec et al. 1992) and in vivo (Bums et al., 1996). Such findings imply that SlgA can promote recovery from viral infections as well as initial protection. Another unique feature of the mucosal immune system compared to the systemic immune system is the induction of antigen-specific B and T cells in IgA inductive organized lymphoid tissues (GALT. BALT. etc.) and their distribution to remote mucosal effector sites (i.e. lamina propria regions of the intestine, bronchi, genitourinary tract and secretory glands). This cellular distribution pathway linking distant mucosal sites is referred to as the common mucosal immune system (Mestecky, 1987). Although originally it was proposed that activated IgA-committed B cells and Thelper (Th) cells traffic equally well to all secretory tissues