Abstract
Lymphatic filariasis can be associated with development of serious pathology in the form of lymphedema, hydrocele, and elephantiasis in a subset of infected patients. Dysregulated host inflammatory responses leading to systemic immune activation are thought to play a central role in filarial disease pathogenesis. We measured the plasma levels of microbial translocation markers, acute phase proteins, and inflammatory cytokines in individuals with chronic filarial pathology with (CP Ag+) or without (CP Ag−) active infection; with clinically asymptomatic infections (INF); and in those without infection (endemic normal [EN]). Comparisons between the two actively infected groups (CP Ag+ compared to INF) and those without active infection (CP Ag− compared to EN) were used preliminarily to identify markers of pathogenesis. Thereafter, we tested for group effects among all the four groups using linear models on the log transformed responses of the markers. Our data suggest that circulating levels of microbial translocation products (lipopolysaccharide and LPS-binding protein), acute phase proteins (haptoglobin and serum amyloid protein-A), and inflammatory cytokines (IL-1β, IL-12, and TNF-α) are associated with pathogenesis of disease in lymphatic filarial infection and implicate an important role for circulating microbial products and acute phase proteins.
Highlights
IntroductionTwo-thirds of the 120 million people infected with Wuchereria bancrofti—the major causative agent of human lymphatic filariasis—have subclinical infections, ,40 million have lymphedema and/or other pathologic manifestations including hydroceles (and other forms of urogenital disease), episodic adenolymphangitis, tropical pulmonary eosinophilia, lymphedema, and (in its most severe form) elephantiasis [1]
Two-thirds of the 120 million people infected with Wuchereria bancrofti—the major causative agent of human lymphatic filariasis—have subclinical infections,40 million have lymphedema and/or other pathologic manifestations including hydroceles, episodic adenolymphangitis, tropical pulmonary eosinophilia, lymphedema, and elephantiasis [1]
Circulating microbial products such as LPS and markers associated with microbial translocation have been shown to play an important role in disease pathogenesis of certain infections like HIV
Summary
Two-thirds of the 120 million people infected with Wuchereria bancrofti—the major causative agent of human lymphatic filariasis—have subclinical infections, ,40 million have lymphedema and/or other pathologic manifestations including hydroceles (and other forms of urogenital disease), episodic adenolymphangitis, tropical pulmonary eosinophilia, lymphedema, and (in its most severe form) elephantiasis [1]. Increased frequencies of activated T cells [8], increased parasite antigen-driven Th1 and Th17 cytokine production [6], increased expression of Toll-like and NOD-like receptors [6], and enhanced TLR signaling through TLR ligand stimulation [5] have all been described when comparisons are made between patients with subclinical infection and those with filarial lymphedema and/ or elephantiasis. Innate immune responses play a prominent role in development of pathology, as evidenced by the occurrence of lymphatic damage in animal models of filarial infection lacking an adaptive immune system [9]
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