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

Doris SC Shim, Heidi C Schilter, Michelle L Knott, Ranni A Almeida, Robert P Short, Charles R Mackay, Lindsay A Dent, William A Sewell

    Research output: Contribution to journalArticleResearchpeer-review

    4 Citations (Scopus)

    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.
    Original languageEnglish
    Pages (from-to)553 - 558
    Number of pages6
    JournalImmunology and Cell Biology
    Volume90
    Issue number5
    DOIs
    Publication statusPublished - 2012

    Cite this

    Shim, D. SC., Schilter, H. C., Knott, M. L., Almeida, R. A., Short, R. P., Mackay, C. R., ... Sewell, W. A. (2012). Protection against Nippostrongylus brasiliensis infection in mice is independent of GM-CSF. Immunology and Cell Biology, 90(5), 553 - 558. https://doi.org/10.1038/icb.2011.69
    Shim, Doris SC ; Schilter, Heidi C ; Knott, Michelle L ; Almeida, Ranni A ; Short, Robert P ; Mackay, Charles R ; Dent, Lindsay A ; Sewell, William A. / Protection against Nippostrongylus brasiliensis infection in mice is independent of GM-CSF. In: Immunology and Cell Biology. 2012 ; Vol. 90, No. 5. pp. 553 - 558.
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    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.",
    author = "Shim, {Doris SC} and Schilter, {Heidi C} and Knott, {Michelle L} and Almeida, {Ranni A} and Short, {Robert P} and Mackay, {Charles R} and Dent, {Lindsay A} and Sewell, {William A}",
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    Shim, DSC, Schilter, HC, Knott, ML, Almeida, RA, Short, RP, Mackay, CR, Dent, LA & Sewell, WA 2012, 'Protection against Nippostrongylus brasiliensis infection in mice is independent of GM-CSF', Immunology and Cell Biology, vol. 90, no. 5, pp. 553 - 558. https://doi.org/10.1038/icb.2011.69

    Protection against Nippostrongylus brasiliensis infection in mice is independent of GM-CSF. / Shim, Doris SC; Schilter, Heidi C; Knott, Michelle L; Almeida, Ranni A; Short, Robert P; Mackay, Charles R; Dent, Lindsay A; Sewell, William A.

    In: Immunology and Cell Biology, Vol. 90, No. 5, 2012, p. 553 - 558.

    Research output: Contribution to journalArticleResearchpeer-review

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    T1 - Protection against Nippostrongylus brasiliensis infection in mice is independent of GM-CSF

    AU - Shim, Doris SC

    AU - Schilter, Heidi C

    AU - Knott, Michelle L

    AU - Almeida, Ranni A

    AU - Short, Robert P

    AU - Mackay, Charles R

    AU - Dent, Lindsay A

    AU - Sewell, William A

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