Atg5 Supports Rickettsia australis Infection in Macrophages In Vitro and In Vivo

Jeremy Bechelli, Leoncio Vergara, Claire Smalley, Tetyana P. Buzhdygan, Sean Bender, William Zhang, Yan Liu, Vsevolod Popov, Jin Wang, Nisha Garg, Seungmin Hwang, David Walker, Rong Fang

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6 Scopus citations

Abstract

Rickettsiae can cause life-threatening infections in humans. Macrophages are one of the initial targets for rickettsiae after inoculation by ticks. However, it remains poorly understood how rickettsiae remain free in macrophages prior to establishing their infection in microvascular endothelial cells. Here, we demonstrated that the concentration of Rickettsia australis was significantly greater in infected tissues of Atg5flox/flox mice than in the counterparts of Atg5flox/flox Lyz-Cre mice, in association with a reduced level of interleukin-1β (IL-1β) in serum. The greater concentration of R. australis in Atg5flox/flox bone marrow-derived macrophages (BMMs) than in Atg5flox/flox Lyz-Cre BMMs in vitro was abolished by exogenous treatment with recombinant IL-1β. Rickettsia australis induced significantly increased levels of light chain 3 (LC3) form II (LC3-II) and LC3 puncta in Atg5-competent BMMs but not in Atg5-deficient BMMs, while no p62 turnover was observed. Further analysis found the colocalization of LC3 with a small portion of R. australis and Rickettsia-containing double-membrane-bound vacuoles in the BMMs of B6 mice. Moreover, treatment with rapamycin significantly increased the concentrations of R. australis in B6 BMMs compared to those in the untreated B6 BMM controls. Taken together, our results demonstrate that Atg5 favors R. australis infection in mouse macrophages in association with a suppressed level of IL-1β production but not active autophagy flux. These data highlight the contribution of Atg5 in macrophages to the pathogenesis of rickettsial diseases.

Original languageEnglish (US)
JournalInfection and Immunity
Volume87
Issue number1
DOIs
StatePublished - Jan 1 2019

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Keywords

  • Atg5
  • autophagosomes
  • IL-1β
  • mouse macrophages
  • Rickettsia australis

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

Bechelli, J., Vergara, L., Smalley, C., Buzhdygan, T. P., Bender, S., Zhang, W., Liu, Y., Popov, V., Wang, J., Garg, N., Hwang, S., Walker, D., & Fang, R. (2019). Atg5 Supports Rickettsia australis Infection in Macrophages In Vitro and In Vivo. Infection and Immunity, 87(1). https://doi.org/10.1128/IAI.00651-18