Determination of murine loci and genes responsible for the natural resistance to Trypanosoma cruzi infection

• Grant number: 10/50959-4
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2011
• End date: January 31, 2013
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Dario Simões Zamboni
• Grantee: Dario Simões Zamboni
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The intracellular protozoan parasite Trypanosoma cruzi is the etiological agent of Chagas Disease, which shows highly variable symptoms and clinical manifestations, which depends on genetic components of the parasites and the vertebrate host. The human resistance against infectious agents such as T. cruzi is usually regulated by multiple genes that control different aspects of the host/parasite interaction. Thus, the identification of these genes in humans is critical for understanding of the host resistance mechanisms, and therefore allows a possible pharmacological intervention aiming the treatment and prevention of the disease. In this scenario, the murine models of infection facilitate the identification of resistance genes since the gene responsible for a given process is usually associated to the corresponding human gene. Therefore, inbred strains of mouse that differ in host resistance can be used as toll for identification of such genes. Here, we aim to infect informative F2 populations from generated from 2 inbred strains of mice to identify loci and genes important for host resistance against T. cruzi infection. After the acquisition of the biological data, we will proceed with the QTL analysis Quantitative Trait Loci), to identify loci and host genes involved with host resistance. These genetic factors will be further investigated to validate the QTL data. The development of the present project may generate relevant information regarding the pathogenesis and host resistance against T. cruzi infection. Furthermore, the dissemination of the knowledge generated here may contribute for future therapeutic intervention aiming the prevention and treatment of Chagas Disease and other tropical infection diseases. (AU)

Scientific publications

(7)

(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)

MOREIRA, LILIAN O.; ZAMBONI, DARIO S.. NOD1 and NOD2 signaling in infection and inflammation. FRONTIERS IN IMMUNOLOGY, v. 3, 2012. (10/50959-4, 12/09363-6)

MASSIS, LILIANA M.; ZAMBONI, DARIO S.. Innate immunity to Legionella pneumophila. FRONTIERS IN MICROBIOLOGY, v. 2, 2011. (10/50959-4)

SANCHES, TIAGO L. M.; CUNHA, LARISSA D.; SILVA, GRACE K.; GUEDES, PAULO M. M.; SILVA, JOAO SANTANA; ZAMBONI, DARIO S.. The Use of a Heterogeneously Controlled Mouse Population Reveals a Significant Correlation of Acute Phase Parasitemia with Mortality in Chagas Disease. PLoS One, v. 9, n. 3, MAR 20 2014. (10/50959-4, 13/08216-2)

PEREIRA, MARCELO S. F.; MORGANTETTI, GIULIANO F.; MASSIS, LILIANA M.; HORTA, CATARINA V.; HORI, JULIANA I.; ZAMBONI, DARIO S.. Activation of NLRC4 by Flagellated Bacteria Triggers Caspase-1-Dependent and -Independent Responses To Restrict Legionella pneumophila Replication in Macrophages and In Vivo. JOURNAL OF IMMUNOLOGY, v. 187, n. 12, p. 6447-6455, DEC 15 2011. (10/50959-4)

SILVA, GRACE KELLY; COSTA, RENATA SESTI; SILVEIRA, TATIANA NUNES; CAETANO, BRAULIA COSTA; HORTA, CATARINA VELTRINI; SALAZAR GUTIERREZ, FREDY ROBERTO; DA MATTA GUEDES, PAULO MARCOS; ANDRADE, WARRISON ATHANASIO; DE NIZ, MARIANA; GAZZINELLI, RICARDO TOSTES; et al. Apoptosis-Associated Speck-like Protein Containing a Caspase Recruitment Domain Inflammasomes Mediate IL-1 beta Response and Host Resistance to Trypanosoma cruzi Infection. JOURNAL OF IMMUNOLOGY, v. 191, n. 6, p. 3373-3383, SEP 15 2013. (10/50959-4, 07/53940-0)

CAETANO, BRAULIA C.; BISWAS, AMLAN; LIMA-JUNIOR, DJALMA S.; BENEVIDES, LUCIANA; MINEO, TIAGO W. P.; HORTA, CATARINA V.; LEE, KYOUNG-HEE; SILVA, JOAO S.; GAZZINELLI, RICARDO T.; ZAMBONI, DARIO S.; et al. Intrinsic expression of Nod2 in CD4(+) T lymphocytes is not necessary for the development of cell-mediated immunity and host resistance to Toxoplasma gondii. European Journal of Immunology, v. 41, n. 12, p. 3627-3631, DEC 2011. (10/50959-4)

SILVA, GRACE K.; CUNHA, LARISSA D.; HORTA, CATARINA V.; SILVA, ALEXANDRE L. N.; GUTIERREZ, FREDY R. S.; SILVA, JOAO S.; ZAMBONI, DARIO S.. A Parent-of-Origin Effect Determines the Susceptibility of a Non-Informative F1 Population to Trypanosoma cruzi Infection In Vivo. PLoS One, v. 8, n. 2, FEB 11 2013. (10/50959-4, 07/53940-0)