Macrophages as effector cells of protective immunity in murine schistosomiasis. V. Variation in macrophage schistosomulacidal and tumoricidal activities among mouse strains and correlation with resistance to reinfection.

Mice of several inbred strains previously characterized as defective in various aspects of macrophage activation for tumor cell killing were utilized to compare the genetic control of induction of macrophage tumoricidal and schistosomulacidal activity and to examine the role of activated macrophages in concomitant immunity to Schistosoma mansoni infection. In all mouse strains tested, macrophage larvicidal activity developed concurrently with tumoricidal activity after in vivo bacillus Calmette Guérin or Corynebacterium parvum treatment. Lpsd strains, A/J, and P/N mice failed to develop macrophages capable of killing either tumor cells or helminth larvae in vitro, whereas C57BL/6J, C3H/HeN, and BALB/c mice all demonstrated strongly cytotoxic cells. In fact, analysis of the reactivity of peritoneal cells from C. parvum-treated F1 hybrids between H-2 congeneic high responder (B10.A) and low responder (A) strains of mice, as well as from F1 hybrid X parent backcross animals, suggested that macrophage activation for killing of these two unrelated extracellular targets is controlled by the same autosomal dominant gene. Strains of mice that failed to develop activated macrophages after in vivo treatment with bacterial stimuli also failed to develop tumoricidal and larvicidal macrophages as a result of S. mansoni infection. The addition of antischistosome sera to the cultures did not reverse the unresponsiveness of macrophages from S. mansoni-infected C3H/HeJ, A/J, or P/N mice in in vitro larvicidal assays. Furthermore, the pattern of concomitant immunity at 6 wk after primary S. mansoni infection correlated closely with the pattern of induction of activated macrophages in these strains of mice. Whereas animals with normal macrophage function developed highly significant levels of concomitant immunity, strains with the Lps defect demonstrated lower levels of acquired resistance, and A/J and P/N mice were not significantly resistant to S. mansoni challenge infection. These results indicate that the genes controlling macrophage activation for the killing of extracellular targets also influence the development of concomitant immunity in schistosomiasis, and suggest that macrophages activated as a consequence of primary S. mansoni infection may be involved in the in vivo effector mechanism of resistance to challenge infection.