| Leukocytes infiltrate the skin and draining lymph nodes in response to the protozoan Leishmania infantum chagasi. | |
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MedLine Citation:
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PMID: 20937764 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The vector-borne protozoan Leishmania infantum chagasi causes minimal inflammation after inoculation into skin but disseminates to cause fatal visceral leishmaniasis. To define the inflammatory response at the parasite inoculation site, we introduced metacyclic L. infantum chagasi promastigotes intradermally into BALB/c mouse ears and studied inflammatory cells over 7 days. Ly6G(+) neutrophils rapidly infiltrated the dermis, peaking after 6 to 24 h. Macrophages and NK cells next infiltrated the dermis, and NK followed by B cells expanded in draining lymph nodes. Parasite-containing phagocytes were tracked with fluorescent mCherry-labeled L. infantum chagasi. Ly6G(+) neutrophils contained the greatest proportion of intracellular parasites 6 to 24 h after inoculation, whereas dermal macrophages harbored the majority of intracellular parasites after 2 to 7 days. These observations were validated microscopically. Low doses of antibody transiently depleted mice of neutrophils, leaving other cells intact. Combined results of in vivo imaging, flow cytometry, and quantitative PCR showed that neutrophil depletion slowed the clearance of extracellular (luciferase-positive) promastigotes during the first 24 h after inoculation yet decreased the numbers of leukocytes containing intracellular (mCherry-positive) parasites. From 3 days onward, total L. infantum chagasi-containing dermal leukocytes and total L. infantum chagasi parasites in draining lymph nodes were similar in both groups. Nonetheless, a second wave of L. infantum chagasi-containing neutrophils occurred 7 days after parasite inoculation into neutrophil-depleted mice, corresponding to the time of neutrophil recovery. Thus, neutrophils were recruited to the dermis even late after inoculation, and L. infantum chagasi trafficked through neutrophils in both neutrophil-depleted and control mice, albeit with different kinetics. Recruitment of neutrophils and transient parasite residence in neutrophils may play a role in nonulcerative forms of leishmaniasis. |
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Authors:
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Colin J Thalhofer; Yani Chen; Bayan Sudan; Laurie Love-Homan; Mary E Wilson |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-10-11 |
Journal Detail:
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Title: Infection and immunity Volume: 79 ISSN: 1098-5522 ISO Abbreviation: Infect. Immun. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2010-12-23 Completed Date: 2011-01-25 Revised Date: 2011-08-01 |
Medline Journal Info:
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Nlm Unique ID: 0246127 Medline TA: Infect Immun Country: United States |
Other Details:
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Languages: eng Pagination: 108-17 Citation Subset: IM |
Affiliation:
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Interdisciplinary Immunology Program, University of Iowa, Iowa City, IA 52242, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Female Leishmania infantum / immunology* Leishmaniasis, Visceral / immunology* Leukocytes / physiology* Lymph Nodes / cytology* Mice Mice, Inbred BALB C Neutrophils Skin / cytology* |
| Grant Support | |
ID/Acronym/Agency:
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R01 AI045540/AI/NIAID NIH HHS; R01 AI045540-09/AI/NIAID NIH HHS; R01 AI067874/AI/NIAID NIH HHS; R01 AI076233/AI/NIAID NIH HHS; T32 AI076233/AI/NIAID NIH HHS |
| Comments/Corrections | |
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