Molecular pathogenesis and subversion of host responses in infections with Legionella spp.

• Grant number: 12/09363-6
• Support Opportunities: Regular Research Grants
• Start date: September 01, 2012
• End date: August 31, 2014
• Field of knowledge: Biological Sciences - Microbiology - Biology and Physiology of Microorganisms
• 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

Bacteria of the Legionella genus were identified as important agents to public health in 1976, being considered as etiological agents of a severe pneumonia known as legionnaire's disease. These infections occur around the world as sporadic cases, outbreaks or hospital infections, where the former presents mortality rate higher than 50%. The pulmonary infection of mouse is the most common experimental model used to investigate both the pathogenesis and the host responses against Legionella. However, flagellin expressed by L. pneumophila activates host cell pathways that lead to restriction of bacterial replication, which transforms mouse and their macrophages resistant to L. pneumophila infection, differently of that observed in humans. Recent studies identified a new species of the Legionella genus called L. longbeachae, which is responsible for 30-50% of infections caused by Legionella in countries of southern hemisphere. L. longbeachae has been shown to be highly virulent and lethal in mice models (similarly to that observed in legionnaire's disease in humans); the genome sequencing revealed absence of flagellin and the presence of several genes potentially related to pathogenesis. In the light of these biological information and because of the high importance of this emergent infectious disease in countries of southern hemisphere, we intend to employ a murine model of infection by L. longbeachae to evaluate: i) genes and bacterial processes that contribute to bacterial pathogens and mice lethality; ii) host responses that contribute to control of the infection and host resistance against life threatening bacterial pneumonia such as legionnaires's disease. (AU)

Scientific publications

(8)

(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)

CUNHA, LARISSA D.; ZAMBONI, DARIO S.. Recognition of Legionella pneumophila nucleic acids by innate immune receptors. Microbes and Infection, v. 16, n. 12, SI, p. 985-990, DEC 2014. (13/08216-2, 14/04684-4, 12/09363-6)

CUNHA, LARISSA D.; ZAMBONI, DARIO S.. Recognition of Legionella pneumophila nucleic acids by innate immune receptors. Microbes and Infection, v. 16, n. 12, p. 6-pg., 2014-12-01. (13/08216-2, 14/04684-4, 12/09363-6)

MASSIS, LILIANA M.; ASSIS-MARQUES, MARIANA A.; CASTANHEIRA, FERNANDA V. S.; CAPOBIANCO, YASMIN J.; BALESTRA, ANDIAMIRA C.; ESCOLL, PEDRO; WOOD, REBECCA E.; MANIN, GRAZIELE Z.; CORREA, VANI M. A.; ALVES-FILHO, JOSE C.; et al. Legionella longbeachae Is Immunologically Silent and Highly Virulent In Vivo. Journal of Infectious Diseases, v. 215, n. 3, p. 440-451, FEB 1 2017. (13/08216-2, 14/04684-4, 10/20600-4, 14/50268-2, 12/09363-6)

MASCARENHAS, DANIELLE P. A.; CERQUEIRA, DAIANE M.; PEREIRA, MARCELO S. F.; CASTANHEIRA, FERNANDA V. S.; FERNANDES, TALITA D.; MANIN, GRAZIELE Z.; CUNHA, LARISSA D.; ZAMBONI, DARIO S.. Inhibition of caspase-1 or gasdermin-D enable caspase-8 activation in the Naip5/NLRC4/ASC inflammasome. PLOS PATHOGENS, v. 13, n. 8, AUG 2017. (13/08216-2, 14/04684-4, 12/09363-6)

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)

CASE, CHRISTOPHER L.; KOHLER, LARA J.; LIMA, JONILSON B.; STROWIG, TILL; DE ZOETE, MARCEL R.; FLAVELL, RICHARD A.; ZAMBONI, DARIO S.; ROY, CRAIG R.. Caspase-11 stimulates rapid flagellin-independent pyroptosis in response to Legionella pneumophila. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v. 110, n. 5, p. 1851-1856, JAN 29 2013. (12/09363-6)

HORI, JULIANA I.; PEREIRA, MARCELO S. F.; ROY, CRAIG R.; NAGAI, HIROKI; ZAMBONI, DARIO S.. Identification and functional characterization of K+ transporters encoded by Legionella pneumophila kup genes. Cellular Microbiology, v. 15, n. 12, p. 2006-2019, DEC 2013. (11/22617-4, 12/09363-6, 11/51023-5)

MASCARENHAS, DANIELLE P. A.; PEREIRA, MARCELO S. F.; MANIN, GRAZIELE Z.; HORI, JULIANA I.; ZAMBONI, DARIO S.. Interleukin 1 Receptor-Driven Neutrophil Recruitment Accounts to MyD88-Dependent Pulmonary Clearance of Legionella pneumophila Infection In Vivo. Journal of Infectious Diseases, v. 211, n. 2, p. 322-330, JAN 15 2015. (13/08216-2, 14/04684-4, 12/09363-6)