Interferon gamma produced by CD4+ T cells during malaria infection is known to be important for elimination of parasites from the host (also known as restriction). In preliminary studies, we have found that CD4+ T cells possess interferon-independent mechanisms of malaria parasite restriction, but the specific molecules involved remain unknown. We also find that phagocytes are critically important for control of acute infection, suggesting that CD4+ T cells may target myeloid cells such as macrophages through interferon-independent mechanisms. We have identified a candidate factor - macrophage colony stimulating factor - that is expressed by CD4+ T cells responding to malaria infection, and is consistent with the increase in macrophage numbers that occurs during malaria infection and their essentiality for anti-parasite activity. The proposed work will determine the role of macrophage colony stimulating factor in restriction of malaria parasites, and determine whether the fraction of this cytokine originating from CD4+ T cells plays a physiologically significant rol in this process. The studies have the potential to identify a significant new mechanism of host protection and a new role for helper T cells in contributing to the immunological control of malaria infection.
Malaria is one of the largest causes of infectious morbidity and mortality in the world. The proposed work examines an aspect of immunity that may be responsible for expanding and activating macrophages, which can then contribute to the clearance of malaria parasites from the host. Understanding this process will shed light on immunity to malaria and may aid vaccine design efforts.
| Williams, Claire R; Baccarella, Alyssa; Parrish, Jay Z et al. (2017) Empirical assessment of analysis workflows for differential expression analysis of human samples using RNA-Seq. BMC Bioinformatics 18:38 |
| Fontana, Mary F; de Melo, Gabrielly L; Anidi, Chioma et al. (2016) Macrophage Colony Stimulating Factor Derived from CD4+ T Cells Contributes to Control of a Blood-Borne Infection. PLoS Pathog 12:e1006046 |
| Williams, Claire R; Baccarella, Alyssa; Parrish, Jay Z et al. (2016) Trimming of sequence reads alters RNA-Seq gene expression estimates. BMC Bioinformatics 17:103 |
