Dennis Hartigan-O'Connor Lab
It has become increasingly clear that (i) mucosal surfaces are important not only in the transmission but also the pathogenesis of lentiviral infections and (ii) development of the immune system at mucosal surfaces is shaped by interaction with the outside world. Our recent research synthesizes these findings and tests how the status of the mucosal immune system at the time of infection may impact upon the pathogenesis of lentiviral disease.
The development and composition of the mucosal immune system has previously been invoked to explain local damage by opportunistic pathogens, repair of normal damage to the mucosal barrier, and susceptibility to systemic autoimmune conditions. For instance, a 2006 publication in Science demonstrated that microbial colonization of mice triggers production of RegIIIγ, a bactericidal lectin that was later shown to mediate the early protective effects of IL-22 against Citrobacter rodentium, an attaching and effacing bacterial pathogen of mice (Cash et al., Science 313:1126, 2006 and Zheng et al., Nature Medicine 14:282, 2008). More recently, Mazmanian et al. showed that presence of the commensal organism, Bacteroides fragilis, protects mice from experimental colitis induced by Helicobacter hepaticus (Nature 453:620, 2008). Given these examples, we are curious if there might be substantial individual variability in intestinal immune cell populations that would affect the inflammatory stance of the host immune system and the subsequent progress of lentiviral infection. Such variability may also influence response to vaccinations or susceptibility to autoimmune disease.