GROWTH OF B MALAYI IN MURINE MODELS--ROLE OF NK CELLS

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Over the past few years, we have been analyzing the course of Brugia malayi infection in numerous murine models. Based on these studies, we propose a hypothsis that B. malayi requires a host derived factor of lymphoid origin for growth and development in the mammalian host. This hypothsis provokes us to re-examine the interaction between the human immune system and B. malayi as a dynamic bi-directional interaction, rather than a pure host protective response. Our data strongly suggest that NK cells are a potential cell source for this factor. In the current proposal, we plan to confirm our hypothesis by repeating some our studies, as well as evaluating the effect of (1) NK cell depletion in susceptible animals and (2) NK cell reconstitution in non-permissive animals on the growth of B. malayi. In addition, we will analyze the kinetics of the loss of B. malayi in non-permissive animals to determine the precise point in its development that the growth factor is required. We also propose to set up in vitro experiments to identify a cell line that will best support the in vitro growth and development of B. malayi. Using standard somatic cell genetic technologies, we will isolate numerous variants from the cell line that no longer support the growth of B. malayi. Using differential display technology, we will determine the mRNA molrcule(s) that is (are) missing in the mutants. Identification of the molecule(s) involved in the interaction could help us formulate a rationale approach to immunoprophylaxis, as well as pharmacology of lymphatic filarial parasites.