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The Wellcome Trust Lecture: Infection and disease in lymphatic filariasis: an immunological perspective

Published online by Cambridge University Press:  06 April 2009

E. A. OtteSen
E. A. OtteSen
Affiliation:
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md 20892, USA
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Summary

The basic tenet of the immunological perspective of fuiarial disease is that differential immune responsiveness among individuals exposed to infection results in the different clinical manifestations that develop. The mechanisms involved in this differential responsiveness appear to reflect different T-cell cytokine response patterns. Asymptomatic patients with the clinically silent presentation of ‘asymptomatic microfilaraemia’, who have been previously described as being ‘immunosuppressed’ with respect to their generating pro-inflammatory (Th1-type) immune responses to parasite antigen, are now recognized to be fully responsive to parasite antigen but to produce cytokines and mediators that have primarily anti-inflammatory (Th2-like) effects. Studies with immunodeficient mice have indicated the existence of two alternative pathways to the development of lymphatic pathology: one dependent on the induction of inflammatory reactions by the host immune response, the other entirely independent of the immune system and reflecting the direct actions of the parasite or its products on the lymphatics. As histopathology of affected human lymphatics is consistent with this hypothesis, it may be that the lymphatic pathology seen normally in the amicrofilaraemic, highly immunoresponsive infected patients derives from inflammation induced by immune responses to parasite antigen, whereas the lymphatic pathology sometimes seen coexisting with the ‘immunosuppressed’ state of asymptomatic microfilaraemia actually reflects lymphatic damage that is not immunologically mediated. Though little information exists about the ‘natural history’ of lymphatic filariasis, there is no evidence for an inevitable progression from one clinical form to another. Instead, there appears to be a definite plasticity in the response that depends on prior (? pre-natal) and current exposure to the parasite as well as on the immunomodulatory effects it induces. This plasticity does not appear to be complete, however, as there is no evidence that a chronically infected host who has developed strong pro-inflammatory immune responses can subsequently become sufficiently ‘down-regulated’ to support an asymptomatic microfilaraemia type of infection. Another possible constraint to the plasticity of the clinical and immunological responses may be the genetic determination of certain unusual syndromes, such as tropical pulmonary eosinophilia or TPE, though this hypothesis remains to be proven.

Keywords

lymphaticfilariasisimmunological perspectivediseaseinfection.
Type
Lymphatic Filariasis
Information
Parasitology , Volume 104 , Issue S1: Symposia of the British Society for Parasitology Volume 29:Human parasitic disease: the complementory roles of field and laboratory studies , June 1992 , pp. S71 - S79
Copyright
Copyright © Cambridge University Press 1992

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