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Programmed death ligand-1 (PD-L1) is a co-signaling molecule that regulates T-cell responses in vivo . Its role in bacterial infections, including Q fever, a zoonosis due to Coxiella burnetii infection, is not well understood. We showed by flow cytometry that PD-L1 membrane expression was specifically increased in T-cells from patients with acute Q fever, not from patients with Q fever endocarditis, suggesting that PD-L1 plays a role in the early phases of C. burnetii infection. To assess this hypothesis, we studied the role of PD-L1 in C. burnetii -infected mice. C. burnetii infection resulted in PD-L1 up-regulation in splenocytes. Anti-PD-L1 antibodies injected into the mice did not affect the total number of splenic T-cells but increased the relative number of CD4 + T-cells compared with CD8 + T-cells. Additionally, anti-PD-L1 antibodies significantly increased the number of splenic CD4 + and CD8 + T cells that expressed low membrane CD62L levels. Our results indicate that the increased expression of PD-L1 by T-cells is associated with a decreased number of memory T-cells during C. burnetii infection, opening new perspectives in the understanding of Q fever pathophysiology. [ABSTRACT FROM AUTHOR]

Abstract: Until now, when a new Rickettsia species was isolated in a tick, it was not possible to predict whether it was a human pathogen or if it would cause a skin eschar at the infection site. Guinea pigs are injected intradermally with 25 different Rickettsia species or subspecies: 16 induced an eschar, 5 induced inflammatory lesions and 4 have no effect. We observed that the occurrence of skin eschars in this model was significantly correlated (P <0.05) with observations of skin eschars in humans (14/16). The most common histological finding was mononuclear cell infiltration. Polymorphonuclear cell infiltration was observed for Rickettsia australis, Rickettsia japonica, and, as in humans, Rickettsia africae. The treatment of guinea pigs with corticosteroids prevents the apparition of eschar following Rickettsia bellii inoculation. Virulent, but not avirulent, Rickettsia prowazekii induced transient inflammatory lesions that were associated with dermal vasculitis, as is Rickettsia typhi. Therefore, the intradermal injection of Rickettsia in guinea pigs appears to be a relevant model for the prediction of the development of escharotic lesions following Rickettsia infection in humans. We speculate that skin eschar is the reflect of a local control avoiding extreme virulence. [Copyright &y& Elsevier]