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.
Rodrigues
Olivia Roos
OR
UEI Leishmanioses, Centro de Malária e Outras Doenças Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 96, 1349-008 Lisbon, Portugal.
Moura
Rita Aguiar
RA
Gomes-Pereira
Sandra
S
Santos-Gomes
Gabriela Maria
GM
D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004198:Disease Susceptibility; D006239:Haplotypes; D006790:Host-Parasite Interactions; D018314:Leishmania infantum / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D007898:Leishmaniasis, Visceral / Q000276:immunology*; D008264:Macrophages / Q000276:immunology / Q000469:parasitology*; D008297:Male; D051379:Mice; D014774:Virulence
D016207:Cytokines