DEVIATION OF IMMUNE-RESPONSE TO CHLAMYDIA-PSITTACI OUTER-MEMBRANE PROTEIN IN LIPOPOLYSACCHARIDE-HYPORESPONSIVE MICE

The outcome of infection is determined by both the quantity and the qu ality of an induced immune response, In particular, it has been demons trated for selected pathogens that induction of T(H)1 or T(H)2 type he lper T-cell subsets determines whether an immune response gives rise t o protective immunity or disease-associated immunopathology. The natur e of the antigen and the type of antigen-presenting cells recruited in the induction of a response are critical factors that influence the q uality of the immune response, Of particular interest in this respect is the immune response to bacterial particles and the impact of cell w all-associated lipopolysaccharide (LPS) on that response, Nonspecific activation of macrophages and B lymphocytes by LPS could skew the phen otype of activated antigen presenting cells and selectively alter the immunoglobulin isotypes and helper T-cell subsets that are induced fol lowing infection, In an initial attempt to detect immune deviation ass ociated with LPS stimulation, we have compared the immunoglobulin isot ypes of antibodies specific for the cysteine-rich outer membrane prote in Omp2 induced in normal and LPS-hyporesponsive mice following immuni zation with Chlamydia psittaci strain guinea pig inclusion conjunctivi tis whole elementary bodies, We report that there is a dramatic shift of Omp2-specific antibody from predominantly immunoglobulin G2a (IgG2a ) isotype in LPS-hyporesponsive mice to high levels of IgG1 isotype in LPS-responder strains, The dependence of the IgG1 isotype shift on th e LPS responder status is linked to the structure of the antigen and i ts natural processing pathway since LPS-hyporesponsive mice are not, i n general, deficient in IgG1 antibody production, In particular, the a ntibody response to purified recombinant Omp2 is predominantly of the IgG1 isotype even in LPS-hyporesponsive mite.