Characterization of inflammatory response in the central nervous system in mouse models of viral and protozoan infection

• Grant number: 16/24856-0
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2017
• End date: February 28, 2019
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Pathology
• Principal Investigator: Paulo César Maiorka
• Grantee: Paulo César Maiorka
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

In the last years, a great majority of knowledge regarding the pathological events and immune response in infectious diseases was obtained from mouse models. Equid herpesvirus type 1 (EHV-1) is a potential emerging pathogen which is recognized worldwide as a cause of neurological disease in equine. However, a fatal and acute meningoencephalitis associated with extensive neuronal necrosis caused by EHV-1 have been reported in other animal species. Neospora caninum is an Apicomplexan protozoan, worldwide known as an agent that causes abortion in cattle. In Brazil, the economic losses due to neosporosis is estimated in U$51,7 million annually in dairy farms, and in U$101 million in beef cattle. Clinically, neosporosis in ruminants is characterized by abortions and recurrent estrus. Meningoencephalitis with gliosis and multifocal areas of necrosis is one of the main pathological features in the central nervous system (CNS) of aborted fetuses and occasionally of adult animals. Little is known about the immune response in CNS, mainly regarding the role of inflammatory mediators and cells during development of EHV-1 and N. caninum encephalitis. Therefore, the aim of the present project is to characterize the innate immune response and the pathological events in the CNS of C57BL/6, BALB/C and C3H/HeJ infected by EHV-1 and N. caninum. For this purpose, the expression of proinflammatory cytokines (IL-1², IL-6, IL-12, IFN-³ and TNF-±), chemokine (CCL-2) and Toll-like receptors (TLR3 and TLR9) will be evaluated by gene expression in the CNS. Inflammatory cells such as TCD4+ and TCD8+ cells, macrophages, microglia and dendritic cells will phenotypically be characterized by flow cytometry. Moreover, the concentration of several serum cytokines and chemokines will be measured. During encephalitis, an evaluation of the inflammatory changes will be performed and correlated with the distribution of EHV-1 and N. caninum within the CNS, which will be evaluated by absolute quantification by qPCR. The data obtained here will clarify important aspects of innate immune response and mechanisms of neuroinflammation during a lethal and acute disease caused by EHV-1 and N. caninum. (AU)

Scientific publications

(6)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

COSTA, R. C.; MESQUITA, L. P.; NUNES, M. V. L.; OLIVEIRA, I. M.; OLIVEIRA, L. F. S.; SOUZA, ALINNE R.; MAIORKA, P. C.; VARASCHIN, M. S.. Neospora caninum bioassay in gerbils using placental tissues from naturally infected goats. Veterinary Parasitology, v. 249, p. 70-73, JAN 15 2018. (16/24856-0, 16/05010-2)

MESQUITA, LEONARDO P.; COSTA, RAFAEL C.; ZANATTO, DENNIS A.; BRUHN, FABIO R. P.; MESQUITA, LAIS L. R.; LARA, M. C. C. S. H.; VILLALOBOS, E. M. C.; MASSOCO, CRISTINA O.; MORI, CLAUDIA M. C.; MORI, ENIO; et al. Equine herpesvirus 1 elicits a strong pro-inflammatory response in the brain of mice. JOURNAL OF GENERAL VIROLOGY, v. 102, n. 3, p. 12-pg., 2021-01-01. (16/24856-0, 16/09396-2)

MESQUITA, LEONARDO P.; COSTA, RAFAEL C.; MESQUITA, LAIS L. R.; LARA, MARIA DO CARMO C. S. H.; VILLALOBOS, ELIANA M. C.; MORI, CLAUDIA M. C.; MORI, ENIO; HOWERTH, ELIZABETH W.; MAIORKA, PAULO C.. Pathogenesis of Equid Alphaherpesvirus 1 Infection in the Central Nervous System of Mice. VETERINARY PATHOLOGY, v. 58, n. 6, p. 1075-1085, NOV 2021. (18/23619-0, 16/24856-0, 16/09396-2)

MESQUITA, LEONARDO P.; COSTA, RAFAEL C.; MESQUITA, LAIS L. R.; LARA, MARIA DO CARMO C. S. H.; VILLALOBOS, ELIANA M. C.; MORI, CLAUDIA M. C.; MORI, ENIO; HOWERTH, ELIZABETH W.; MAIORKA, PAULO C.. Pathogenesis of Equid Alphaherpesvirus 1 Infection in the Central Nervous System of Mice. VETERINARY PATHOLOGY, JUN 2021. (18/23619-0, 16/09396-2, 16/24856-0)

MESQUITA, LEONARDO P.; COSTA, RAFAEL C.; ZANATTO, DENNIS A.; BRUHN, FABIO R. P.; MESQUITA, LAIS L. R.; LARA, M. C. C. S. H.; VILLALOBOS, E. M. C.; MASSOCO, CRISTINA O.; MORI, CLAUDIA M. C.; MORI, ENIO; et al. quine herpesvirus 1 elicits a strong pro-inflammatory response in the brain of mic. JOURNAL OF GENERAL VIROLOGY, v. 102, n. 3, 2021. (16/24856-0, 16/09396-2)

COSTA, RAFAEL CARNEIRO; MESQUITA, LEONARDO PEREIRA; DE OLIVEIRA JR, IVAM MOREIRA; ZANNATO, DENNIS ALBERT; DOS SANTOS MESQUITA, LUCAS EMANUEL; BIIHRER, DANIEL ARRAIS; MASSOCO SALLES GOMES, CRISTINA DE OLIVEIRA; VARASCHIN, MARY SUZAN; MAIORKA, PAULO CESAR. The pathogenicity of two Neospora caninum goat strains in a BALB/c mouse model. Experimental Parasitology, v. 205, OCT 2019. (16/05010-2, 16/24856-0)