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Protection against Nippostrongylus brasiliensis infection in mice is independent of GM-CSF

Abstract

Granulocyte macrophage-colony stimulating factor (GM-CSF) is a cytokine with the capacity to promote inflammation in a wide variety of infectious and inflammatory diseases. These conditions include allergic airway inflammation, which is driven by T-helper 2 (Th2) cells. Because of the importance of Th2 cells in parasite infections, we have investigated the role of GM-CSF in mice infected with the nematode Nippostrongylus brasiliensis. The effect of primary and secondary infection was investigated in mice lacking functional genes for GM-CSF (CSF2 genes) (DeltaGM-CSF mice), and in mice lacking the cytokine receptor common beta chain (Deltabeta mice), the latter being unable to signal in response to GM-CSF and interleukin (IL)-5. DeltaGM-CSF mice showed no significant defect in parasite immunity, measured by larval numbers in the lungs, worm numbers in the intestine or egg numbers in the faeces, in either primary or secondary infection. By contrast, the Deltabeta mice showed increased parasite burden, with higher numbers of lung larvae after secondary infection and higher numbers of intestinal worms and faecal eggs after both primary and secondary infection. Unexpectedly, there were increased numbers of circulating eosinophils in the DeltaGM-CSF mice, associated with significantly reduced larval numbers in the lungs. These results indicate that GM-CSF is redundant in protection against N. brasiliensis infection, and that the increased susceptibility of Deltabeta mice to infection is likely to be attributed to the lack of IL-5 signalling in these mice. The results suggest that clinical use of agents that neutralise GM-CSF may not be associated with increased risk of parasite infection.Immunology and Cell Biology advance online publication, 16 August 2011; doi:10.1038/icb.2011.69.

Type Journal
Authors Shim, D. S.; Schilter, H. C.; Knott, M. L.; Almeida, R. A.; Short, R. P.; Mackay, C. R.; Dent, L. A.; Sewell, W. A.
Garvan Authors A/Prof William Sewell
Publisher Name IMMUNOL CELL BIOL
Published Date 2012-08-17 00:00:00
Published Volume 90
Published Issue 5
Published Pages 553-8
URL http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21844882
Status Published In-print
OpenAccess Link https://publications.gimr.garvan.org.au/download.php?11129_11884/Shim.pdf