Infection with the Lyme disease pathogen suppresses innate immunity in mice with diet-induced obesity.
Zlotnikov N1, Javid A1, Ahmed M1, Eshghi A1, Tang TT1, Arya A1, Bansal A1, Matar F1, Parikh M1, Ebady R1, Koh A1, Gupta N1, Song P1, Zhang Y1, Newbigging S2, Wormser GP3, Schwartz I4, Inman R5, Glogauer M1, Moriarty TJ6,7.
Obesity is a major global public health concern. Immune responses implicated in obesity also control certain infections. We investigated the effects of high fat diet (HFD)-induced obesity (DIO) on infection with the Lyme disease bacterium Borrelia burgdorferi in mice. DIO was associated with systemic suppression of neutrophil- and macrophage-based innate immune responses. These included bacterial uptake and cytokine production, and systemic, progressive impairment of bacterial clearance and increased carditis severity. B. burgdorferi-infected mice fed normal diet also gained weight at the same rate as uninfected mice fed HFD, Toll-like receptor 4 deficiency rescued bacterial clearance defects, which were greater in females than males, and killing of an unrelated bacterium (Escherichia coli) by bone marrow-derived macrophages from obese, B. burgdorferi-infected mice was also affected. Importantly, innate immune suppression increased with infection duration and depended on cooperative and synergistic interactions between DIO and B. burgdorferi infection. Thus, obesity and B. burgdorferi infection cooperatively and progressively suppressed innate immunity in mice.