Functional comparison of innate immune signaling pathways in primates

Humans respond differently than other primates to a large number of infections. differences in susceptibility to infectious agents between humans and other primates are probably due to inter-species differences in immune response to infection. consistent with that notion,genes involved in immunity-related processes are strongly enriched among recent targets of positive selection in primates,suggesting that immune responses evolve rapidly,yet providing only indirect evidence for possible inter-species functional differences. to directly compare immune responses among primates,we stimulated primary monocytes from humans,chimpanzees,and rhesus macaques with lipopolysaccharide (lps) and studied the ensuing time-course regulatory responses. we find that,while the universal toll-like receptor response is mostly conserved across primates,the regulatory response associated with viral infections is often lineage-specific,probably reflecting rapid host-virus mutual adaptation cycles. additionally,human-specific immune responses are enriched for genes involved in apoptosis,as well as for genes associated with cancer and with susceptibility to infectious diseases or immune-related disorders. finally,we find that chimpanzee-specific immune signaling pathways are enriched for hiv-interacting genes. put together,our observations lend strong support to the notion that lineage-specific immune responses may help explain known inter-species differences in susceptibility to infectious diseases. © 2010 barreiro et al.