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.

• Document type: Journal article
• Source: Journal of Infectious Diseases; v. 215, n. 3, p. 440-451, FEB 1 2017.
• Web of Science Citations: 4

Abstract

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)

• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 14/04684-4 - The inflammasome in the host response against intracellular pathogens and the microbial mechanisms for its evasion
• Grantee: Dario Simões Zamboni
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 10/20600-4 - Study of asthma prevention and treatment with the administration of viable and heat-killed Saccharomyces cerevisiae in a murine model of allergic asthma
• Grantee: Marcos de Carvalho Borges
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 14/50268-2 - Deciphering the interactions between Legionella longbeachae and eukaryotic host cells
• Grantee: Dario Simões Zamboni
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/09363-6 - Molecular pathogenesis and subversion of host responses in infections with Legionella spp.
• Grantee: Dario Simões Zamboni
• Support Opportunities: Regular Research Grants