International Cytokine & Interferon Society

Keke Fairfax – 2021 ICIS Regeneron New Investigator is tomorrow’s Global Immunotalk presenter

Global Immunotalks Live on Wednesdays 9AM PST, 12PM EST, 4PM GMT

ZOOM LINK: https://ucsd.zoom.us/j/91053505061

Q&A via TWITTER with #globalimmuno (contingent on speaker availability)

All talks are recorded and uploaded in YouTube channel named “Global Immunotalks” https://www.youtube.com/c/GLOBALIMMUNOTALKS

December 14 Keke Fairfax “To protect a host: Unwinding the mechanisms of helminth antigens in reprogramming of host immunity”

Keke C. Fairfax, PhD
Associate Professor and Director of Equity, Diversity, and Inclusion
Division of Microbiology and Immunology
Department of Pathology
University of Utah

Research

IL-4 and immuno-modulation are hallmarks of parasitic infections. Dr. Fairfax’s laboratory broadly focuses on using the helminth parasite Schistosoma mansoni as a tool to understand both, the consequences of IL-4 induced immuno-modulation, and the complex interplay between B, T and stromal cells necessary to develop an optimal T and B cell memory response. Under this umbrella they currently have three main projects: 1) Understanding the immunological implications of maternal schistosomiasis; 2) Dissecting the role of IL-4 in shaping the cellular environment of peripheral lymph nodes during homeostasis and antigenic challenge; 3) Delineating the mechanistic role of hepatic macrophages in helminth-induced protection from metabolic diseases.

Project 1: 

The relative efficacy of many life-saving immunizations is often significantly lower in resource-poor countries relative to the developed world. Although this reduction is undoubtedly multifactorial, there is strong evidence that the chronic presence of prenatal and early childhood parasitic infections undermines the development of effective immune responses to certain antigens through an inappropriate polarization of the immune response. At least 10 million women in Africa have been diagnosed with this helminth infection during pregnancy. Exposure to these highly immunogenic antigens has been shown to lead to both immune priming and immunomodulation. However, a major gap exists in our understanding of how prenatal antigen exposure and treatment of Schistosoma mansoni impacts the subsequent immune responsiveness of offspring. Dr. Fairfax’s lab has established a model of maternal S. mansoni infection in IL-4 dual reporter 4get/KN2 mice that allows them to effectively determine in vivo alterations in IL-4 production. This model has revealed that maternal S. mansoni infection leads to the development of a schistosome egg antigen (SEA) specific immune response in offspring and profound alterations to CD21/35 expression on B cells and follicular dendritic cells, a scenario which is likely to lead reduced generation and retention of germinal center and memory B cells.

Project 2: 

Infection by pathogens that range from parasites to bacteria elicits vigorous antibody responses critical for host protection. It is clear that optimal humoral immune responses depend on T follicular helper (TFH) cells, lymphatic endothelial cells (LECs), and follicular dendritic cells (FDCs), which are subsets of immune cells that form direct, or cognate, interactions with B cells in secondary lymphoid organs to promote germinal center formation, isotype class-switching, and affinity maturation of the B cell receptor. While these cell types have recently been well-characterized, there remains a dearth of knowledge about the role of cytokines in driving their maintenance and expansion under both homeostatic and inflammatory conditions. Dr. Fairfax’s lab recently identified a role for IL-4 in the homeostatic maintenance of both FDCs and LECs in peripheral lymph nodes, as well as their expansion following immunization with both SEA and tetanus/diphtheria. 

Project 3:

An increasing body of literature has established an inverse correlation between chronic helminth infections (e.g., trematodes, roundworms) and inflammatory diseases such as asthma, inflammatory bowel disease, and, importantly, metabolic syndrome and diabetes. Murine models of Schistosoma mansoni infection have demonstrated that both patent infection and exposure to SEA leads to lower levels of total serum cholesterol and a beneficial increase in the ratio of HDL to LDL cholesterol, reducing atherogenesis and plaque size in the ApoE CVD/atherosclerosis model. Despite strong evidence that a history of Schistosome infection exerts a protective effect against the development of metabolic syndrome, obesity, and CVD, a major gap exists in our understanding of the mechanism(s) underlying this protection. We have recently identified that S. mansoni infection induces profound transcriptional alterations in global metabolic pathways of hepatic macrophages, including changes to phospholipid and cholesterol metabolism, as well as, amino acid biosynthesis and glucagon signaling. Dr. Fairfax’s future work will focus on establishing the heritability of S. mansoni induced metabolic changes in the monocyte/macrophage lineage, and their ability to protect from metabolic disorders. Her long-term goal for this area of research is to use schistosome infection as a tool to identify novel immunological pathways for treatment of insulin resistance and atherosclerosis.

joefner@cytokinesociety.org
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