H-2 Complex Influences Cytokine Gene Expression in Leishmania Infantum-infected Macrophages

This work aims to study the influence of H-2 locus in the control of Leishmania infantum infection by evaluating whether cytokine responses by host macrophages of different H-2 haplotype are differentially regulated, either induced or actively impaired during parasite growth and replication. This study shows that macrophages of "non-cure" phenotype (H-2(d)) are more susceptible to infection with virulent L. infantum promastigotes. Virulent parasites lead to impaired IL-12 and inhibited TNF-alpha expression. The degree of parasite virulence is an important contributing factor to differences detected in cytokine expression. Virulent parasites also induced TGF-beta, a deactivating cytokine that is known to suppress Th-1 type responses, thus allowing the parasite to subvert antimicrobial activity and increase its chances of survival. Depending on specific host haplotype, cells differentially respond to infection since TNF-alpha expression is inhibited and TGF-beta is enhanced by macrophages of "non-cure" phenotype, thus perhaps determining their degree of susceptibility in this strain of mice.