Key inflammatory mediators drive the resolution of acute Lyme disease

Abstract

Lyme disease is an inflammatory disease in response to Borrelia burgdorferi infection. We analyzed cytokines in sera from acute and convalescent LD patients and also evaluated the effect of these mediators on human monocytes. Different inflammatory mediators were measured in human sera obtained during active disease and convalescence, as well as from healthy controls. IL-12, IFN-gamma, and soluble TNF receptors were elevated in acute LD sera, which returned to normal levels during convalescence. MMP-1 levels, however, continued to be elevated. Convalescence sera showed a decrease in the secretion of sIL6R, IL-26, IL-2, and IFN-alpha, which were also elevated in acute LD but dropped during convalescence. Decreased levels of anti-inflammatory, Th2- and M2 polarization-associated cytokines sCD163, IFN-β, and IL-10 did not change during acute LD but decreased during convalescence. As multiple pathways are turned on and off during acute and convalescence, we performed a serum transcriptomics approach on human monocytes exposed to these sera. Differential expression of proinflammatory genes, endosomal proteins, type I IFN-related genes, and interferon-dependent genes was observed. In cells exposed to convalescent sera, genes such as CXCL3 and CCL20 did not return to their baseline levels. Our results help to elaborate a better understanding of the inflammatory processes involved in the progression of acute and the resolution of LD.