Legionella longbeachae Is Immunologically Silent and Highly Virulent In Vivo

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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. ; Cunha, Fernando Q. ; Buchrieser, Carmen ; Borges, Marcos C. ; Newton, Hayley J. ; Zamboni, Dario S.

• Tipo de documento: Artigo Científico
• Fonte: Journal of Infectious Diseases; v. 215, n. 3, p. 440-451, FEB 1 2017.
• Citações Web of Science: 4

Resumo

Background. Legionella longbeachae (Llo) and Legionella pneumophila (Lpn) are the most common pneumonia-causing agents of the genus. Although both species can be lethal to humans and are highly prevalent, little is known about the molecular pathogenesis of Llo infections. In murine models of infection, Lpn infection is self-limited, whereas Llo infection is lethal. Methods. We used mouse macrophages, human macrophages, human epithelial cells, and mouse infections in vivo to evaluate multiple parameters of the infection. Results. We determined that the Llo Dot/Icm secretion system is critical for virulence. Different than Lpn, Llo disseminates and the animals develop a severe pulmonary failure, as demonstrated by lung mechanics and blood oxygenation assays. As compared to Lpn, Llo is immunologically silent and fails to trigger the production of cytokines in human pulmonary epithelial cells and in mouse and human macrophages. Infections in Tnfr1-/-, Ifng-/-, and Il12p40-/-mice supported the participation of cytokines for the resistance phenotype. Conclusions. Both Lpn and Llo require the Dot/Icm system for pathogenesis, but the infection outcome is strikingly different. Llo is immunologically silent, highly virulent, and lethal. The differences reported herein may reflect unappreciated clinical differences in patients infected with Lpn or Llo. (AU)

• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 14/04684-4 - O inflamassoma na resposta contra patógenos intracelulares e os mecanismos microbianos relacionados à evasão
• Beneficiário: Dario Simões Zamboni
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 10/20600-4 - Estudo da prevenção e tratamento da asma induzida por alérgeno em um modelo animal com a administração de Saccharomyces cerevisiae vivas e inativadas pelo calor
• Beneficiário: Marcos de Carvalho Borges
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 14/50268-2 - Deciphering the interactions between Legionella longbeachae and eukaryotic host cells
• Beneficiário: Dario Simões Zamboni
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 12/09363-6 - Patogênese molecular e subversão das respostas do hospedeiro em infecções por Legionella spp.
• Beneficiário: Dario Simões Zamboni
• Modalidade de apoio: Auxílio à Pesquisa - Regular