Adipose tissue serves as a reservoir for recrudescent Rickettsia prowazekii infection in a mouse model.
Brill-Zinsser disease, the relapsing form of epidemic typhus, typically occurs in a susceptible host years or decades after the primary infection; however, the mechanisms of reactivation and the cellular reservoir during latency are poorly understood. Herein we describe a murine model for Brill-Zinsser disease, and use PCR and cell culture to show transient rickettsemia in mice treated with dexamethasone >3 months after clinical recovery from the primary infection. Treatment of similarly infected mice with cyclosporine failed to produce recrudescent bacteremia. Therapy with doxycycline for the primary infection prevented recrudescent bacteremia in most of these mice following treatment with dexamethasone. Rickettsia prowazekii (the etiologic agent of epidemic typhus) was detected by PCR, cell culture, and immunostaining methods in murine adipose tissue, but not in liver, spleen, lung, or central nervous system tissues of mice 4 months after recovery from the primary infection. The lungs of dexamethasone-treated mice showed impaired expression of beta-defensin transcripts that may be involved in the pathogenesis of pulmonary lesions. In vitro, R. prowazekii rickettsiae infected and replicated in the murine adipocyte cell line 3T3-L1. Collectively these data suggest a role for adipose tissue as a potential reservoir for dormant infections with R. prowazekii.
Bechah
Yassina
Y
Unit for Research on Emergent and Tropical Infectious Diseases (URMITE), CNRS-IRD UMR 6236, Faculty of Medicine, University of the Mediterranean, Marseille, France.
Paddock
Christopher D
CD
Capo
Christian
C
Mege
Jean-Louis
JL
Raoult
Didier
D
D000273:Adipose Tissue / Q000382:microbiology*; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D003907:Dexamethasone / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D008168:Lung / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012283:Rickettsia prowazekii / Q000302:isolation & purification*; D014438:Typhus, Epidemic Louse-Borne / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology*; D023083:beta-Defensins / Q000378:metabolism
D017931:DNA Primers; D023083:beta-Defensins; D003907:Dexamethasone