immunology of infectious and parasitic diseases - XXXVII Congress ...
immunology of infectious and parasitic diseases - XXXVII Congress ...
immunology of infectious and parasitic diseases - XXXVII Congress ...
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INNATE AND ADAPTIVE IMMUNE REPONSE AGAINST LEISHMANIA<br />
INFECTION IS DEPENDENT ON NOD-LIKE RECEPTORS ACTIVATION<br />
DJALMA S. LIMA-JUNIOR 1,2 , EULÁLIA L. SILVA 2 , FERNANDA MARIM 1,2 ,<br />
SILVIA ULIANA 3 , JOÃO S. SILVA 2 , DARIO S. ZAMBONI 2<br />
1- Department <strong>of</strong> Cell Biology, School <strong>of</strong> Medicine <strong>of</strong> Ribeirão Preto, University<br />
<strong>of</strong> São Paulo, Ribeirão Preto, São Paulo, Brazil<br />
2- Department <strong>of</strong> Biochemistry <strong>and</strong> Immunology, School <strong>of</strong> Medicine <strong>of</strong> Ribeirão<br />
Preto, University <strong>of</strong> São Paulo, Ribeirão Preto, São Paulo, Brazil<br />
3- Department <strong>of</strong> Parasitology, Institute <strong>of</strong> Biomedical Sciences, University <strong>of</strong><br />
São Paulo, São Paulo, Brazil.<br />
Abstract<br />
Introduction: The intracellular sensors Nod1 <strong>and</strong> Nod2 have key role in the<br />
host responses. During activation, these proteins signals via the adapter<br />
molecule Rip2, which is a protein kinase that leads to activation <strong>of</strong> NF-κB <strong>and</strong><br />
MAPK favoring the production <strong>of</strong> cytokines <strong>and</strong> chemokines. Also, Nod1 <strong>and</strong><br />
Nod2 participate in the detection/control <strong>of</strong> several pathogens as they sense<br />
PAMPs contained in the cell walls <strong>of</strong> Gram-negative <strong>and</strong> Gram-positive<br />
bacteria. However, the role <strong>of</strong> Nod1 <strong>and</strong> Nod2 during Leishmania infection is<br />
unknown. Aim: Here, we investigated the participation <strong>of</strong> Nod/Rip2 pathway in<br />
host response during L. major infection. Methods: Bone marrow macrophage<br />
(BMDMs) or –dendritic cells (BMDCs) derived from C57BL/6, Nod1 -/- , Nod2 -/-<br />
<strong>and</strong> Rip2 -/- mice were infected with L. major promastigotes <strong>and</strong> cytokines<br />
(ELISA/flow cytometry) <strong>and</strong> NO (Griess assay) production, surface molecules<br />
expression (flow cytometry) <strong>and</strong> killing (Giemsa staining) were analyzed.<br />
Additionally, the lesion development <strong>and</strong> parasite burden were measured in<br />
WT-, Nod1 -/- -, Nod2 -/- - <strong>and</strong> Rip2 -/- -infected mice. Dendritic cells activation <strong>and</strong><br />
cytokines production were evaluated at 8 th week p.i. by flow cytometry. Finally,<br />
we analyzed the susceptibility <strong>and</strong> cytokines production in chimeras generated<br />
by irradiating recipient mice. Results: Nod1 -/- , Nod2 -/- <strong>and</strong> Rip2 -/- BMDMs had<br />
an impaired induction <strong>of</strong> NF-κB–dependent products in response to infection<br />
<strong>and</strong> failed to restrict L. major replication. Moreover, IL-12p40 production <strong>and</strong><br />
surface molecules expression were decreased in parasite infected-Rip2 -/-<br />
BMDCs. Nod1 activation was crucial for in vivo parasite replication control <strong>and</strong>
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