Infection with the Lyme disease pathogen suppresses innate immunity in mice with diet-induced obesity

Abstract

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-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 high-fat diet, toll-like receptor 4 deficiency rescued bacterial clearance defects, which greater in female than male mice, 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.

The gut microbiota in infants of obese mothers increases inflammation and susceptibility to NAFLD

“…In addition to hepatic inflammation, Inf-ObMB-colonized mice demonstrated a dysfunctional BMDM phenotype. The macrophages isolated from Inf-ObMB mice were hypo-responsive to LPS and had reduced ability to phagocytize Listeria , features consistent with an impaired anti-inflammatory, reparative macrophage phenotype 51 . Of interest, the reduced BMDM function was maintained even after differentiation in vitro for 7 days, suggesting that the dysbiotic Inf-ObMB gives rise to altered development of myeloid cell precursors.…”

Comparison of spleen transcriptomes of two wild rodent species reveals differences in the immune response against Borrelia afzelii

“…In each enrichment plot, the score at the peak of the plot (the score furthest from 0.0) is the enrichment score for the gene set. of these pro-inflammatory cytokines in skin and blood is up-regulated during the early phase of Borrelia infection (Bouquet et al, 2016;Jones et al, 2008;Müllegger et al, 2000;Zlotnikov et al, 2017). In contrast, expression of for example TNFα in tissues from late-stage Borrelia infection in mice was reduced (Hodzic, Feng, & Barthold, 2013).…”

Lipid Profiles in Lyme Borreliosis: A Potential Role for Apheresis?

“…Given the evidence that [1] lipids are implicated in the pathogenesis and severity of Lyme disease and its complications [2], and the fact that elevated LDL and triglycerides are a significant risk factor (particularly in combination with inflammation) for cardiovascular disease, and [3] the documented risk of patients with Lyme disease for other atherosclerosis, ischemic strokes and carditis [17,18] and, [4] finally, the role of cardiometabolic disturbances, including obesity and dyslipidemia, may suppress innate immunity and allow neuroborreliosis [19,20]. These data clearly justify the need for further studies providing individualized and effective treatment for this patient group.…”