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immunology of infectious and parasitic diseases - XXXVII Congress ...

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SITE OF L. MAJOR INFECTION DETERMINES DOMINANT HOST CELL<br />

PHENOTYPE<br />

ERIC HENRIQUE ROMA 1,2 , FLÁVIA RIBEIRO-GOMES 1 , DAVID SACKS 1 ,<br />

NATHAN PETERS 1 .<br />

1 National Institutes <strong>of</strong> Allergy <strong>and</strong> Infectious Diseases, NIH – Bethesda, USA<br />

2 Institute <strong>of</strong> Biological Sciences, Universidade Federal de Minas Gerais - Belo<br />

Horizonte, Brazil<br />

Introduction: The impact <strong>of</strong> the inoculation site on the outcome <strong>of</strong> infection with<br />

the intracellular parasite Leishmania is poorly understood. We investigated the<br />

acute interactions between L. major <strong>and</strong> phagocytic cells at different sites <strong>of</strong><br />

infection commonly used in studies <strong>of</strong> Leishmaniasis.<br />

Methods <strong>and</strong> results: C57BL/6 mice were infected with L. major expressing<br />

red fluorescent protein (RFP) by the subcutaneous (footpad) <strong>and</strong> intradermal<br />

(ear) routes. At 2 <strong>and</strong> 48 hours post-infection, ears <strong>and</strong> footpads showed similar<br />

numbers <strong>of</strong> CD11b + cells, where as ears had higher numbers on day 9. At all<br />

time points tested, the number <strong>of</strong> infected cells was higher in the ear versus the<br />

footpad. Phenotyping <strong>of</strong> RFP + cells revealed that the dominant infected<br />

population in the ear were neutrophils at 2h, inflammatory monocytes at 48h,<br />

<strong>and</strong> inflammatory <strong>and</strong> Ly6C low monocytes at 9 days post infection. In the<br />

footpad, infected cells were predominantly macrophages/dendritic cells<br />

(MΦ/DC) at 2h, Ly6C low monocytes at 48h, <strong>and</strong> MΦ/DC at 9 days. Infection in<br />

the ear was associated with higher levels <strong>of</strong> IL-10 <strong>and</strong> CXCL1 mRNA versus the<br />

footpad. Conclusion: The acute interaction between L. major <strong>and</strong> phagocytic<br />

cells is different at different sites <strong>of</strong> infection. These observations may help to<br />

explain divergent observations in studies <strong>of</strong> Leishmaniasis that employ different<br />

inoculation sites.<br />

Financial support: NIH <strong>and</strong> CAPES.

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