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) (DGM-CSF mice), and in mice lacking the cytokine receptor common b chain (Db mice), the latter being unable to signal in response to GM-CSF and interleukin (IL)-5. DGM-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 Db 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 DGM-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 Db 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.

Genomic perspectives on adaptation and conservation in the endangered long-tailed goral (Naemorhedus caudatus)

“…A critical component of the immune response, Type 2 T helper cells (T H 2) are believed to have evolved to combat extracellular parasites and are the primary immune response to helminthiasis 30-33 , which has been shown to cause mortality among captive gorals 14 . Among the T H 2 PSGs identified in the long-tailed goral, interleukin 5 ( IL5 ) is a T H 2 cytokine known to play critical roles in the immune response to extracellular parasitic infections.…”

Intracerebral GM-CSF contributes to transendothelial monocyte migration in APP/PS1 Alzheimer’s disease mice

“…51 This cytokine is produced by numerous different cell types in response to cytokine or inflammatory stimuli and is involved in peripheral cell migration.…”

Dendritic cells in Th2 immune responses and allergic sensitization

“…93 Thus, the precise role of GM-CSF in allergic sensitization remains unclear, as also suggested by reports that GM-CSF-KO mice generate normal protective Th2 responses to the helminth parasite Nippostrongylus brasiliensis. 94 cDC-expressed molecules that are associated with the priming of Th2 responses Several molecules have been shown to be expressed in cDCs during allergic sensitization and are associated with an improved ability to prime allergic responses ( Figure 2).…”