Innate immune receptors in canine visceral leishmaniasis
Innate immune receptors, Canine visceral leishmaniasis, Leishmania infantum, TOLL like receptors (TLRs), NOD like receptors (NLRs).
Dogs are the primary reservoirs of parasites of the Leishmania genus. Innate immune receptors perform early detection of the parasite and lead to specific adaptive immune response in attempt to infection control. However, few studies have investigated a correlation between the expression of innate immunity receptors and the resistance or susceptibility pattern in dogs naturally infected with Leishmania infantum. The aim of this study was to correlate the clinical status of dogs naturally infected with L. infantum with the expression levels of innate imune receptors: Toll like receptors-TLRs (TLR1-9), non-inflamasome forming Nod Like receptors-NLRs (NOD1 e NOD2), inflamasome forming NLRs (NLRP1 e NLRP3), cytokines (IL1β, IL-6, IL-12, IL-10, TNFα, IFN-γ) and iNOS in the liver using real-time PCR. Liver and serum samples were collected from 57 dogs naturally infected by L. infantum at the Zoonoses Control Center in Natal, Rio Grande do Norte, Brazil. The infection was confirmed by ELISA, DPP® tests and imprint of the spleen. Subsequently, fifty-seven dogs were clinically evaluated and classified as asymptomatic (n = 19), oligosymptomatic (19) or symptomatic (n = 19). The results demonstrate the increased expression of all TLRs, NLRs and inflamasome in dogs naturally infected by L. infantum compared with uninfected animals. However, symptomatic dogs showed higher expression of TLR1, TLR2, TLR3, TLR4, TLR5, TLR7, TLR8 NLRP1, NLRP3, NOD1 and IL-1β than asymptomatic animals, revealing significant up regulation of transcription with disease progression. On the other hand, asymptomatic dogs presented greater cytokine mRNA expression (IFN-γ, IL-12) and iNOS when compared to oligosymptomatic and asymptomatic animals. This study unveil new knowledge involving innate immunity receptors (TLRs, NLRs, NLRPs) and cytokines in canine visceral leishmaniasis and may be used as a basis for better understanding of resistance or susceptibility mechanisms in dogs infected with L. infantum, as well as prophylactic strategies to control canine visceral leishmaniasis.