title: Responses of murine and human macrophages to leptospiral infection: a study using comparative array analysis.
abstract: Leptospirosis is a re-emerging tropical infectious disease caused by pathogenic Leptospira spp. The different host innate immune responses are partially related to the different severities of leptospirosis. In this study, we employed transcriptomics and cytokine arrays to comparatively calculate the responses of murine peritoneal macrophages (MPMs) and human peripheral blood monocytes (HBMs) to leptospiral infection. We uncovered a series of different expression profiles of these two immune cells. The percentages of regulated genes in several biological processes of MPMs, such as antigen processing and presentation, membrane potential regulation, and the innate immune response, etc., were much greater than those of HBMs (>2-fold). In MPMs and HBMs, the caspase-8 and Fas-associated protein with death domain (FADD)-like apoptosis regulator genes were significantly up-regulated, which supported previous results that the caspase-8 and caspase-3 pathways play an important role in macrophage apoptosis during leptospiral infection. In addition, the key component of the complement pathway, C3, was only up-regulated in MPMs. Furthermore, several cytokines, e.g. interleukin 10 (IL-10) and tumor necrosis factor alpha (TNF-alpha), were differentially expressed at both mRNA and protein levels in MPMs and HBMs. Some of the differential expressions were proved to be pathogenic Leptospira-specific regulations at mRNA level or protein level. Though it is still unclear why some animals are resistant and others are susceptible to leptospiral infection, this comparative study based on transcriptomics and cytokine arrays partially uncovered the differences of murine resistance and human susceptibility to leptospirosis. Taken together, these findings will facilitate further molecular studies on the innate immune response to leptospiral infection.
authors.affiliation: Beijing Friendship Hospital, Capital Medical University, Beijing, China ; Beijing Tropical Medicine Research Institute, Beijing, China ; Beijing Key Laboratory for Research on Prevention and Treatment of Tropical Diseases, Beijing, China ; Beijing Institute of Biotechnology, Beijing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xue
authors.forename: Xinghui
authors.initials: X
authors.lastname: Zhao
authors.forename: Yingchao
authors.initials: Y
authors.lastname: Yang
authors.forename: Jinping
authors.initials: J
authors.lastname: Zhao
authors.forename: Yutao
authors.initials: Y
authors.lastname: Yang
authors.forename: Yongguo
authors.initials: Y
authors.lastname: Cao
authors.forename: Cailing
authors.initials: C
authors.lastname: Hong
authors.forename: Yuan
authors.initials: Y
authors.lastname: Liu
authors.forename: Lan
authors.initials: L
authors.lastname: Sun
authors.forename: Minjun
authors.initials: M
authors.lastname: Huang
authors.forename: Junchao
authors.initials: J
authors.lastname: Gu
mesh_terms: D000818:Animals; D054884:Host-Pathogen Interactions; D006801:Humans; D007919:Leptospira / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D046228:Microarray Analysis