Immunopathogenesis of lymphatic filarial disease

Abstract

Although two-thirds of the 120 million people infected with lymph-dwelling filarial parasites 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. Adult filarial worms reside in the lymphatics and lymph nodes and induce changes that result in dilatation of lymphatics and thickening of the lymphatic vessel walls. Progressive lymphatic damage and pathology results from the summation of the effect of tissue alterations induced by both living and nonliving adult parasites, the host inflammatory response to the parasites and their secreted antigens, the host inflammatory response to the endosymbiont Wolbachia, and those seen as a consequence of secondary bacterial or fungal infections. Inflammatory damage induced by filarial parasites appears to be multifactorial, with endogenous parasite products, Wolbachia, and host immunity all playing important roles. This review will initially examine the prototypical immune responses engendered by the parasite and delineate the regulatory mechanisms elicited to prevent immune-mediated pathology. This will be followed by a discussion of the proposed mechanisms underlying pathogenesis, with the central theme being that pathogenesis is a two-step process - the first initiated by the parasite and host innate immune system and the second propagated mainly by the host’s adaptive immune system and by other factors (including secondary infections).

New developments in clinical aspects of lymphatic disease

“…In filariasis, progression of lymphedema, and therefore elephantiasis (the gross tissue changes seen in advanced lymphedema giving rise to skin resembling elephant hide), is considered a two-step process -the first initiated by the filarial parasite and host innate immune system and the second propagated by the host's adaptive immune system and secondary infection (30). With an estimated 120 million people infected by lymph-dwelling filarial parasites, 40 million have lymphedema and secondary infections, thereby creating an enormous global disease burden.…”

In-vitro Evaluation of Thymol Derived from Trachyspermum ammi against Acetaminophen Induced Hepatotoxicity Towards Lymphatic Filariasis Therapeutics

“…Recurrent episodes of bacterial infections further damage the tiny lymphatic vessels in the skin, reducing their ability to drain fluid efficiently. Nevertheless LF is associated with the elevated levels of pro-inflammatory and profibrotic cytokines [2]. Notably, the expression of genes involved in cellular adhesion, inflammation and lymphangiogenesis were altered.…”

“…Existing data support the involvement of pro-inflammatory cytokines namely Interleukin-6 (IL-6) and Interleukin-8 (IL-8) were significantly elevated in LF [2], which plays a key role in the initiation of irreversible swelling, fibrosis [11,12] and regenerative processes of hepatic structure and function [13,14]. Hence, we investigated the potential abilities of thymol against hepatotoxicity, bacterial infection; oxidative stress, elevated cytokines and inflammatory markers expression in response to paracetamol induced effects in WRL-68 liver cells.…”

Immunology of Lymphatic Filariasis

“…The importance of proinflammatory cytokines, possibly of innate origin, in the pathogenesis of lymphedema, has been further strengthened by a series of studies in humans in either the early or late stages or lymphedema. Studies have shown that individuals with chronic lymphatic pathology have elevated levels of C-reactive protein (an acute phase protein, indicating an acute inflammatory response), pro-inflammatory cytokines such as TNF-α, IL-6 and soluble TNF receptor, endothelin-1, IL-2, as well as IL-8, MIP-1α, MIP-1β, MCP-1, TARC and IP-10 in the peripheral circulation (6). Similarly, while patients with both acute and chronic manifestations of LF have elevated circulating levels of IL-6 and IL-8, only those with chronic disease manifestations have elevated levels of sTNF receptors (63).…”