Viable Coxiella burnetii Induces Differential Cytokine Responses in Chronic Q Fever Patients Compared to Heat-Killed Coxiella burnetii.

Cytokine responses of chronic Q fever patients to the intracellular bacterium have mostly been studied using stimulation of immune cells with heat-killed due to the extensive measures needed to work with viable biosafety level 3 agents. Whether research with heat-killed can be translated to immune responses to viable is imperative for the interpretation of previous and future studies with heat-killed Peripheral blood mononuclear cells (PBMCs) of chronic Q fever patients ( = 10) and healthy controls ( = 10) were stimulated with heat-killed or viable of two strains, Nine Mile and the Dutch outbreak strain 3262, for 24 h, 48 h, and 7 days in the absence or presence of serum containing anti- antibodies. When stimulated with viable , PBMCs of chronic Q fever patients and controls produced fewer proinflammatory cytokines (interleukin-6 [IL-6], tumor necrosis factor alpha, and IL-1β) after 24 h than after stimulation with heat-killed In the presence of Q fever seronegative serum, IL-10 production was higher after stimulation with viable rather than heat-killed ; however, when incubating with anti- antibody serum, the effect on IL-10 production was reduced. Levels of adaptive, merely T-cell-derived cytokine (gamma interferon, IL-17, and IL-22) and CXCL9 production were not different between heat-killed and viable stimulatory conditions. Results from previous and future research with heat-killed should be interpreted with caution for innate cytokines, but heat-killed -induced adaptive cytokine production is representative of stimulation with viable bacteria.