THE RELATIVE IMPACT OF BACTERIAL VIRULENCE AND HOST GENETIC BACKGROUND ON CYTOKINE EXPRESSION DURING MYCOBACTERIUM-AVIUM INFECTION OF MICE

Resistance to Mycobacterium avium depends on both genetically encoded macrophage functions and acquired T-cell immunity. Cytokines may play a role in either type of resistance. We studied the expression of inte rleukin-2 (IL-2), IL-4 and interferon-gamma (IFN-gamma) in naturally s usceptible BALB/c (Bcg(s)) and naturally resistant C.D2 (Bcg(r)) conge nic mice infected with two strains of M. avium (one highly virulent an d another of low virulence). We observed that cytokine expression patt erns correlated better with the virulence of the micro-organism than w ith the genetic background of the host. The control of the infection b y the low virulence strain in either mouse strain was associated with an increased expression of IFN-gamma and IL-2. Only Bcg(s) mice infect ed with a virulent strain of M. avium were unable to restrict bacteria l growth. an increased expression of IL-4, early during infection, was detected in the course of the latter infection but played no role in determining the susceptibility to infection. Neutralization of IFN-gam ma or IL-2 with specific monoclonal antibodies led to an exacerbation of the infection in Bcg(r) mice by the two strains of M. avium and in Bcg(s) mice infected with the low virulence strain of M. avium.