Immunology, mast cells, helminth, microbiome, Th2,

Parasitic gastrointestinal nematodes induce potent Th2 responses that both clear intestinal infections and regulate immunity in extraintestinal sites. The innate cellular and molecular drivers of Th2 immunity appear to vary among nematode infections, and the identification of mechanisms that initiate Th2 responses are critical. Key roles for pattern recognition receptors, including Toll-like receptors (TLRs), Nod-like receptors (NLR), and C-type lectins, have been described for Th2 responses, although a central paradigm of Th2 activation that parallels that of TLR/interleukin-12 (IL-12) and Th1 immunity has yet to be defined. TLR4 has been implicated in Th2 immunity in several different systems, including the response to parasitic worms, ovalbumin-lipopolysaccharide, and house dust mite allergen. MyD88 is a signaling adaptor molecule that propagates the response to most TLRs, as well as responses to IL-1 family members, including IL-18 and IL-33.  In contrast IL-1β production plays a role in promoting the chronicity of intestinal helminth infection through its ability to suppress helminth-induced IL-25 and IL-33, resulting in attenuated type 2 immunity.

We will use two models of gastrointestinal helminth infection, Trichinella spiralis and Heligmosomoides polygyrus.  We will analyse the effects of treatments with TLR ligands on the expression of IL-25, IL-33, immunopathology and induction of protective immune responses to the parasite.  Furthermore we will determine the role of IL-33 by examining the response of mice deficient in the receptor for IL-33.

Histology, ELISA, tissue culture, in vivo biology, FACS, confocal microscopy, 2 photon microscopy, IVIS, parasitology

Sharpe T, Farren P, Howieson S, Tuohy P, McQuillan J. 2015.  Occupant interactions and effectiveness of natural ventilation strategies in contemporary new housing in Scotland, UK.  International Journal of Environmental Research and Public Health 12:8480-8497

McSharry C., Vesper S., Wymer L., Howieson S., Chaudhuri R., Wright G.R., Thomson N.C. 2015

Decreased FEV1% in asthmatic adults in Scottish homes with high environmental relative moldiness index values.  Clinical and Experimental Allergy, (2015)  http://dx.doi.org/10.1111/cea.12482

Howieson S. 2014 Are our homes making us ill? The impact of energy efficiency on indoor air quality.  Perspectives in Public Health Vol 134, pp. 318-319, (2014)