MCDB










host-parasite interactions in human filarial nematode diseases

Kenneth Nelson, Ph.D.

Lecturer and Research Scientist
Email: kenneth.nelson@yale.edu
Room: KBT 716
Phone: (203) 432-5013

The past few years my research has emphasized the host-parasite inter-actions in human filariasis. (Filariasis is a family of diseases caused by infection of filarial nematodes. Two disease manifestations of filariasis are "River blindness" and elephantiasis.). We (D.L. Greiner, L.D. Shultz, T.V. Rajan and myself) have developed an animal model for human filariasis using the SCID mouse. Using this model we have studied several factors influencing these diseases including 1) the influence of gender on susceptibility (Men are more likely to become infected than are women.), 2) induction of immune tolerance to filariasis during lactation or transplacentally (Children of infected mothers are more likely to become infected than are children of uninfected mothers.), 3) the influence of genetic background on pathology (SCID or nude mice of different inbred strains show a difference in degree of pathology when infected by the parasites.).

Knockout mice have been very useful for studies of the host-parasite relation-ship. We have determined that mice lacking beta-2 microglobulin (which therefore lack all Class I antigen presenting molecules, and therefore also lack all CD8+ T cells) are able to kill all infective stage larvae injected into them. (This is not too surprising since filarial nematodes are extracellular parasites, and Class I restricted CTLs are normally active against intracellular parasites such as viruses.) The reciprocal experiment, injecting filariae into CD4+ knockout mice, presented a surprise in that these mice were also able to kill all of the injected nematodes. This finding verifies and expands the theory that both lineages of T cells (CD8+ and CD4+) have subsets of cells possessing CTL and helper functions.

In addition to the animal interactions, we have used the methods of molecular biology to identify, clone, express, and test nematode proteins that are candidates for the development of a vaccine against filarial infection.

I teach a unique and very interesting course--a research laboratory (Biology 312La and 313La). This lab course emphasizes a hands on approach to learning the most advanced techniques in molecular biology. What makes this course so interesting is the fact that the students taking the course actually do a research project that is taken from a lab of one of the faculty members of the Department of MCDB. The advantage of this approach is that not only do the students learn the techniques of molecular biology, they also learn the flow (including successes and failures) of real research. Some of the methods done in past labs are: RNA isolation, cDNA synthesis, PCR amplification, Northern and Southern hybridization, cDNA library screening, DNA sequencing, and computer analysis of DNA sequences.

Selected Publications

Nelson, F.K., D.L. Greiner, L.D. Shultz, and T.V. Rajan (1991). The immuno-deficient SCID mouse as model for human lymphatic filariasis. J. Exp Med. 173:659-663.

Rajan, T.V., F.K. Nelson, L.D. Shultz, B.H. Koller, and D.L. Greiner. (1992). CD8+ T lymphocytes are not required for murine resistance to human filarial parasites. J. Parasitol. 78:744-746

Rajan, T.V., J.M. Bailis, J.A. Yates, L.D. Shultz, D.L.Greiner, , F. K. Nelson (1994). Maternal influence on susceptibility of offspring to Brugia malayi infection in a murine model of filariasis. Acta Tropica. 58:283-289.

Yates, J.A., K.A. Schmitz, F.K. Nelson, T.V. Rajan (1994). Infectivity and normal development of third stage Brugia malayi maintained. J. Parasitology. 80:891-894.

Rajan, T.V., F. K. Nelson, L.D. Shultz, K.L. Shultz, W.G. Beamer, J.A. Yates, D.A. Greiner (1994). Influence of gonadal steroids on susceptibility to Brugia malayi in SCID mice. Acta Tropica. 56:307-314.

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