Pregnancy enhances the innate immune response in experimental cutaneous leishmaniasis through hormone-modulated nitric oxide production

Yaneth Osorio, Diana L. Bonilla, Alex-Giovanny Peniche-Trujillo, Peter Melby, Bruno Travi

Research output: Contribution to journalArticle

31 Citations (Scopus)

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 realtime 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.

Original languageEnglish (US)
Pages (from-to)1413-1422
Number of pages10
JournalJournal of Leukocyte Biology
Volume83
Issue number6
DOIs
StatePublished - Jun 1 2008
Externally publishedYes

Fingerprint

Cutaneous Leishmaniasis
Innate Immunity
Nitric Oxide
Estrogens
Nitric Oxide Synthase
Hormones
Leishmania
Pregnancy
Cricetinae
Neutrophils
Macrophages
Infection
Leishmania guyanensis
Parasites
Lymph Nodes
Peritoneal Macrophages
Infection Control
Up-Regulation
Maintenance
Polymerase Chain Reaction

Keywords

  • Estrogen
  • Hamster
  • Leishmania

ASJC Scopus subject areas

  • Cell Biology

Cite this

@article{a5cd05a1662f49019a1fe62ba864e503,
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 na{\"i}ve macrophages, as increased transcription was evident by realtime 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.",
keywords = "Estrogen, Hamster, Leishmania",
author = "Yaneth Osorio and Bonilla, {Diana L.} and Alex-Giovanny Peniche-Trujillo and Peter Melby and Bruno Travi",
year = "2008",
month = "6",
day = "1",
doi = "10.1189/jlb.0207130",
language = "English (US)",
volume = "83",
pages = "1413--1422",
journal = "Journal of Leukocyte Biology",
issn = "0741-5400",
publisher = "FASEB",
number = "6",

}

TY - JOUR

T1 - Pregnancy enhances the innate immune response in experimental cutaneous leishmaniasis through hormone-modulated nitric oxide production

AU - Osorio, Yaneth

AU - Bonilla, Diana L.

AU - Peniche-Trujillo, Alex-Giovanny

AU - Melby, Peter

AU - Travi, Bruno

PY - 2008/6/1

Y1 - 2008/6/1

N2 - 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 realtime 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.

AB - 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 realtime 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.

KW - Estrogen

KW - Hamster

KW - Leishmania

UR - http://www.scopus.com/inward/record.url?scp=45949100431&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=45949100431&partnerID=8YFLogxK

U2 - 10.1189/jlb.0207130

DO - 10.1189/jlb.0207130

M3 - Article

C2 - 18347075

AN - SCOPUS:45949100431

VL - 83

SP - 1413

EP - 1422

JO - Journal of Leukocyte Biology

JF - Journal of Leukocyte Biology

SN - 0741-5400

IS - 6

ER -