Abstract
Q fever endocarditis, a severe complication of Q fever, is associated with a defective immune response, the mechanisms of which are poorly understood. We hypothesized that Q fever immune deficiency is related to altered distribution and activation of circulating monocyte subsets. Monocyte subsets were analyzed by flow cytometry in peripheral blood mononuclear cells from patients with Q fever endocarditis and controls. The proportion of classical monocytes (CD14+CD16− monocytes) was similar in patients and controls. In contrast, the patients with Q fever endocarditis exhibited a decrease in the non-classical and intermediate subsets of monocytes (CD16+ monocytes). The altered distribution of monocyte subsets in Q fever endocarditis was associated with changes in their activation profile. Indeed, the expression of HLA-DR, a canonical activation molecule, and PD-1, a co-inhibitory molecule, was increased in intermediate monocytes. This profile was not restricted to CD16+ monocytes because CD4+ T cells also overexpressed PD-1. The mechanism leading to the overexpression of PD-1 did not require the LPS from C. burnetii but involved interleukin-10, an immunosuppressive cytokine. Indeed, the incubation of control monocytes with interleukin-10 led to a higher expression of PD-1 and neutralizing interleukin-10 prevented C. burnetii-stimulated PD-1 expression. Taken together, these results show that the immune suppression of Q fever endocarditis involves a cross-talk between monocytes and CD4+ T cells expressing PD-1. The expression of PD-1 may be useful to assess chronic immune alterations in Q fever endocarditis.
Highlights
Q fever is a widespread zoonosis caused by Coxiella burnetii, a small gram-negative bacterium
Using CD14 and CD16 monoclonal Abs (mAbs), we analyzed the distribution of monocyte subsets in controls and patients with Q fever endocarditis after the exclusion of debris, doublets and dead cells
These results show that the minor monocyte subsets and the Treg population were affected in Q fever endocarditis
Summary
Q fever is a widespread zoonosis caused by Coxiella burnetii, a small gram-negative bacterium. Humans usually contract Q fever via aerosols and develop a primary infection that is symptomatic in a minority of exposed individuals. Primary Q fever consists of isolated fever, hepatitis or pneumonia [1]. Q fever may become chronic in patients with valvular damage, immunocompromised patients and pregnant women [2]. The major clinical manifestation of chronic Q fever is an endocarditis, which accounts for 48% of blood culture-negative cases of infective endocarditis [3]. Patients with Q fever endocarditis exhibit spontaneous evolution to death in the absence of antibiotic treatment, and long-lasting treatment is not sufficient to prevent relapses [1]. Antibiotic prophylaxis of patients with acute Q fever and valvulopathy prevents the evolution from acute Q fever to endocarditis [4]
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