title: Pregnancy enhances the innate immune response in experimental cutaneous leishmaniasis through hormone-modulated nitric oxide production.
abstract: The maintenance of host defense during pregnancy may depend on heightened innate immunity. We evaluated the immune response of pregnant hamsters during early infection with Leishmania (Viannia) panamensis, a cause of American cutaneous leishmaniasis. At 7 days post-infection, pregnant animals showed a lower parasite burden compared with nonpregnant controls at the cutaneous infection site (P=0.0098) and draining lymph node (P=0.02). Resident peritoneal macrophages and neutrophils from pregnant animals had enhanced Leishmania killing capacity compared with nonpregnant controls (P=0.018 each). This enhanced resistance during pregnancy was associated with increased expression of inducible NO synthase (iNOS) mRNA in lymph node cells (P=0.02) and higher NO production by neutrophils (P=0.0001). Macrophages from nonpregnant hamsters infected with L. panamensis released high amounts of NO upon estrogen exposure (P=0.05), and addition of the iNOS inhibitor L-N6-(1-iminoethyl) lysine blocked the induction of NO production (P=0.02). Infected, nonpregnant females treated with estrogen showed a higher percentage of cells producing NO at the infection site than controls (P=0.001), which correlated with lower parasite burdens (P=0.036). Cultured macrophages or neutrophils from estrogen-treated hamsters showed significantly increased NO production and Leishmania killing compared with untreated controls. iNOS was identified as the likely source of estrogen-induced NO in primed and naïve macrophages, as increased transcription was evident by real-time PCR. Thus, the innate defense against Leishmania infection is heightened during pregnancy, at least in part as a result of estrogen-mediated up-regulation of iNOS expression and NO production.
authors.affiliation: Department of Medicine, University of Texas, Health Science Center, San Antonio, TX 78229-3900, USA.
authors.forename: Yaneth
authors.initials: Y
authors.lastname: Osorio
authors.forename: Diana L
authors.initials: DL
authors.lastname: Bonilla
authors.forename: Alex G
authors.initials: AG
authors.lastname: Peniche
authors.forename: Peter C
authors.initials: PC
authors.lastname: Melby
authors.forename: Bruno L
authors.initials: BL
authors.lastname: Travi
mesh_terms: D000818:Animals; D006224:Cricetinae; D016207:Cytokines / Q000096:biosynthesis; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D007113:Immunity, Innate; D016773:Leishmaniasis, Cutaneous / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000032:analysis; D011247:Pregnancy; D015597:Pregnancy Complications, Parasitic / Q000276:immunology*; D011278:Pregnanes / Q000494:pharmacology
chemical_list: D016207:Cytokines; D004967:Estrogens; D011278:Pregnanes; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II