REGULATION OF HOST IMMUNE-RESPONSES BY MODIFICATION OF SALMONELLA VIRULENCE GENES

Modifying bacterial virulence genes to probe the nature of host immuni ty is mostly unexplored. Here we investigate whether host immune respo nses can be regulated by modification of bacterial virulence genes. In mice, attenuated Salmonella mutant strains with clinical relevance el icited differential host immune responses. Oral administration of a mu tant strain with a PhoP-null phenotype promoted potent innate immune r esponses of macrophages that were sufficient for host defense. In cont rast, administration of an Aro(-) mutant strain elicited stronger spec ific antibody and T-helper (Th)-cell responses, wherein Th1-type cells were required for clearance. Thus, genetic manipulation of bacteria m ay be used to broadly alter immune mechanisms that regulate attenuatio n within the host and to tailor host immunity to specific bacterial pa thogens.