title: Deficiency of prolactin-inducible protein leads to impaired Th1 immune response and susceptibility to Leishmania major in mice.
abstract: Although the strategic production of prolactin-inducible protein (PIP) at several ports of pathogen entry into the body suggests it might play a role in host defense, no study has directly implicated it in immunity against any infectious agent. Here, we show for the first time that PIP deficiency is associated with reduced numbers of CD4(+) T cells in peripheral lymphoid tissues and impaired CD4(+) Th1-cell differentiation in vitro. In vivo, CD4(+) T cells from OVA-immunized, PIP-deficient mice showed significantly impaired proliferation and IFN-γ production following in vitro restimulation. Furthermore, PIP-deficient mice were highly susceptible to Leishmani major infection and failed to control lesion progression and parasite proliferation. This susceptibility was associated with impaired NO production and leishmanicidal activity of PIP KO macrophages following IFN-γ and LPS stimulation. Collectively, our findings implicate PIP as an important regulator of CD4(+) Th1-cell-mediated immunity.
authors.affiliation: Department of Immunology, College of Medicine, University of Manitoba, Winnipeg, MB, Canada; Institute of Tropical Medicine, Third Military Medical University, Chongqing, China.
authors.forename: Jintao
authors.initials: J
authors.lastname: Li
authors.forename: Dong
authors.initials: D
authors.lastname: Liu
authors.forename: Zhirong
authors.initials: Z
authors.lastname: Mou
authors.forename: Olivia C
authors.initials: OC
authors.lastname: Ihedioha
authors.forename: Anne
authors.initials: A
authors.lastname: Blanchard
authors.forename: Ping
authors.initials: P
authors.lastname: Jia
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Myal
authors.forename: Jude E
authors.initials: JE
authors.lastname: Uzonna
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D004198:Disease Susceptibility / Q000276:immunology; D007111:Immunity, Cellular / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology; D008070:Lipopolysaccharides; D008264:Macrophages / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D009569:Nitric Oxide / Q000096:biosynthesis; D010047:Ovalbumin; D011506:Proteins / Q000235:genetics / Q000276:immunology*; D018417:Th1 Cells / Q000166:cytology* / Q000276:immunology*; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D011506:Proteins; C483459:SMGP-PIP protein, mouse; D009569:Nitric Oxide; D007371:Interferon-gamma; D010047:Ovalbumin
keywords: IFN-γ; Leishmania; Macrophages; Protozoan; Th1 cells