Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Humans living in areas where filariasis is endemic vary greatly in their exposure to mosquito-borne infective third-stage larvae (L3) of these parasitic helminths. Because the intensity of exposure to Ags affects T cell differentiation and susceptibility to parasitic infections in murine models, we compared T cell and cytokine responses in 97 residents of two villages in Papua New Guinea, where transmission intensity of Wuchereria bancrofti differed by 63-fold (37 vs 2355 L3 per person per year). Residents of the high transmission village had 4- to 11-fold lower proliferation and IFN-gamma responses to filarial Ags, nonparasite Ag, and PHA by PBMC compared with the low transmission village (p < 0.01) even when subjects were matched for intensity of infection. In contrast, filarial Ag-driven IL-5 production was 5.5-fold greater (p < 0.001), and plasma IL-4 and TGF-beta levels were 4-fold and 34% higher, respectively, in residents of the high transmission village. IL-4 and IL-10 responses by PBMC differed little according to village, and increased production of the counterregulatory cytokines IL-10 or TGF-beta by PBMC did not correlate with weak proliferation and IFN-gamma responses. Plasma IL-5, IFN-gamma, and IL-10 levels were similar in the two villages. These data demonstrate that the intensity of exposure to L3 affects lymphocyte responsiveness and cytokine bias possibly by a mechanism that alters APC function.
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PMID:Transmission intensity determines lymphocyte responsiveness and cytokine bias in human lymphatic filariasis. 1139 Apr 95

Lymphatic filariasis is a significant public health problem in several Pacific island countries. Papua New Guinea is one of the most populous countries in this region, and 39% of its residents are estimated to be infected with Wuchereria bancrofti. The Ministries of Health of the 22 islands and territories in the Pacific region are committed to taking action against lymphatic filariasis. Accordingly, a regional collaborative effort aimed at the control of filariasis has been organized under the auspices of a program referred to as PacELF. The main objective of PacELF is to eliminate filariasis as public health problem in the Pacific region by the year 2010, 10 years before global elimination of this infectious disease has been targeted. This contribution describes the epidemiology and ecological features of filariasis and prospects for its elimination in Papua New Guinea. The frequencies of microfilaremia, chronic lymphatic disease, and acute filarial morbidity in Papua New Guinea are higher than in many other endemic countries of the Pacific, Africa, and South America. All possible combinations of these three manifestations of filariasis exist. They occur independently of each other, and there is no association between chronic lymphatic disease and microfilarial status. Anopheles punctulatus mosquitoes are the main vectors throughout the country. Transmission intensity is heterogeneous and a major determinant of local patent infection and morbidity rates. Annual transmission potential and annual infective biting rates are positively associated with the village-specific microfilarial rate, mean intensity of microfilaremia, and prevalence of leg edema. Children and adults have similar worm burdens, assessed by circulating filarial antigen levels, in areas of high transmission, whereas worm burdens increase with age in areas of lower transmission. Intensity of exposure to infective third-stage larvae (L3) is significantly correlated with filarial antigen-specific lymphocyte proliferation and cytokine production, possibly by a mechanism that alters APC function. Historical evidence suggests that residual insecticide spraying conducted for malaria control in some parts of the country interrupted transmission of W. bancrofti as it did in the Solomon Islands. Prospects for eliminating lymphatic filariasis in Papua New Guinea are good and may be achieved by the end of the second decade of the twenty-first century if an integrated control approach using mass drug administration with vector control is adopted.
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PMID:Lymphatic filariasis in Papua New Guinea: prospects for elimination. 1259 58

To assess the physiologic interactions between the infective stage of Brugia malayi--one of the extracellular parasites responsible for lymphatic filariasis in humans--and the APC with which they come in contact during their development and routes of travel, we have investigated the interaction between the infective stage (L3) of B. malayi and human Langerhans cells (LC) in the skin. Our data indicate that live L3 result in increased migration of LC from the epidermis without affecting the viability of these cells and up-regulation of the IL-18 cytokine involved in LC migration. Live L3 also result in down-regulation of MHC class I and II on the LC cell surface. Additionally, microarray data indicate that live L3 significantly down-regulated expression of IL-8 as well as of multiple genes involved in Ag presentation, reducing the capacity of LC to induce CD4(+) T cells in allogeneic MLR, and thus resulting in a decreased ability of LC to promote CD4(+) T cell proliferation and production of IFN-gamma and IL-10. These data suggest that L3 exert a down-regulatory response in epidermal LC that leads to a diminished capacity of these cells to activate CD4(+) T cells.
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PMID:Filaria-induced immune evasion: suppression by the infective stage of Brugia malayi at the earliest host-parasite interface. 1512 11

Lymphatic filariasis is a disease characterized by immune dysregulation involving APC and T cell populations. To assess the contribution of TLR in mediating this dysregulation, we examined the expression of TLR1, TLR2, TLR4, and TLR9 on B cells and monocytes of filaria-infected and uninfected individuals. Baseline expression of TLR was significantly lower in B cells but not in monocytes of the filaria-infected group compared with the uninfected group. Upon stimulation with filarial Ag, a diminished up-regulation of TLR was observed in both B cells and monocytes of infected individuals. Finally, stimulation of B cells and monocytes with TLR ligands resulted in decreased B cell and monocyte activation/cytokine production, indicating a state of immune tolerance. This dysregulation is associated with diminished CD4(+) T cell production of IFN-gamma and IL-5. The diminished expression and function of TLR is thus a likely consequence of chronic Ag stimulation and could serve as a novel mechanism underlying the dysfunctional immune response in filariasis.
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PMID:Diminished expression and function of TLR in lymphatic filariasis: a novel mechanism of immune dysregulation. 1600 19