Journal of Bacteriology & Parasitology

The interface of the host antiviral response and the infection by Leishmania amazonensis: Role of RNA sensors and Phlebovirus coinfection

5^th International Conference on PARASITOLOGY & MICROBIOLOGY

July 12-13, 2018 Paris, France

Ulisses Gazos Lopes

Federal University of Rio de Janeiro, Brazil

Keynote: J Bacteriol Parasitol

Abstract:

PKR (dsRNA activated kinase) activation, a key regulator of the antiviral pathway, occurs in L. amazonensis infection, leading to the expression of IL-10 and IFN1beta and favoring the parasite intracellular growth. Importantly, the immune staining of human cutaneous Leishmaniasis lesions revealed impressive high levels of IFN1beta/PKR positive cells from patients with untreatable diffuse cutaneous Leishmaniasis. We have investigated whether the endosome dsRNA receptor, TLR3, shared a similar role in L.amazonensis infection. The intracellular growth of the parasites was reduced in TLR3-/- macrophages and this phenomenon was accompanied by significantly reduced levels of IFN1beta and IL-10 and increased levels of IL-12. These data prompted us to test the hypothesis that arboviruses, RNA arthropods transmitted viruses, would interfere with the Leishmania infection. To tackle this hypothesis, we worked with Phlebovirus, a sub group of the Bunyaviridae, which is transmitted by sandflies. We tested a viral isolate of the rodent Nectomys sp., a natural sylvatic reservoir of L. amazonensis from the Amazon region. Leishmania and Phlebovirus coinfection led to high intracellular parasite growth. Importantly, this effect required PKR, TLR3 and IFN1 signaling. L.amazonensis and Phlebovirus synergize the expression of IFN1beta and IL-10. However, the coinfection of L. amazonensis with the ssRNA arbovirus (DENVII) did not induce these effects. Altogether, our data revealed that the classical antiviral cellular responses mediated by PKR and TLR3 are subverted by L.amazonensis. We predict that specific RNA viral coinfections may enhance and sustain the activation of cellular RNA sensors, resulting in the aggravation of the parasite infection.

Biography :

Ulisses Gazos Lopes is an Associate Professor at the Instituto de Biofísica Carlos Chagas Filho, Federal University of Rio de Janeiro, Brazil. He completed his MSc in Parasitology from the Federal University of Minas Gerais, Brazil and obtained his PhD in Genetics from Federal University of Rio de Janeiro, Brazil. He was a Research Fellow at Harvard School of Public Health, Boston, US, from 1984 to1986. He did his Post-doctoral training from the Dana-Farber Cancer Institute/Harvard Medical School, Boston, US. Currently, he is a Visiting Researcher at Institut Pasteur, Paris, France.

E-mail: uligazos@gmail.com