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 L. Popov, Jin Wang, Nisha Garg, Seungmin Hwang, David H. Walker, Rong Fang

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


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 Atg5 flox/flox mice than in the counterparts of Atg5 flox/flox Lyz-Cre mice, in association with a reduced level of interleukin-1 (IL-1) in serum. The greater concentration of R. australis in Atg5 flox/flox bone marrow-derived macrophages (BMMs) than in Atg5 flox/flox Lyz-Cre BMMs in vitro was abolished by exogenous treatment with recombinant IL-1. 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-1 production but not active autophagy flux. These data highlight the contribution of Atg5 in macrophages to the pathogenesis of rickettsial diseases.

Original languageEnglish (US)
Article numbere00651
JournalInfection and immunity
Issue number1
StatePublished - Jan 1 2019


  • Atg5
  • Autophagosomes
  • IL-1
  • Mouse macrophages
  • Rickettsia australis

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases


Dive into the research topics of 'Atg5 supports Rickettsia australis infection in macrophages in vitro and in vivo'. Together they form a unique fingerprint.

Cite this