ILC2s and T cells cooperate to ensure maintenance of M2 macrophages for lung immunity against hookworms.
Defining the immune mechanisms underlying protective immunity to helminth infection remains an important challenge. Here we report that lung CD4(+) T cells and Group 2 innate lymphoid cells (ILC2s) work in concert to block Nippostrongylus brasiliensis (Nb) development in the parenchyma within 48 h in mice. Immune-damaged larvae have a striking morphological defect that is dependent on the expansion of IL-13-producing ILC2 and CD4(+) T cells, and the activation of M2 macrophages. This T-cell requirement can be bypassed by administration of IL-2 or IL-33, resulting in expansion of IL-13-producing ILC2s and larval killing. Depletion of ILC2s inhibits larval killing in IL-2-treated mice. Our results broaden understanding of ILC2's role in immunity to helminths by demonstrating that they not only act as alarmin sensors, but can also be sustained by CD4(+) T cells, ensuring both the prompt activation and the maintenance of IL-13-dependent M2 macrophage immunity in the lung.
Malaghan Institute of Medical Research, Wellington 6242, New Zealand.
Tiffany
T
Bouchery
1] Malaghan Institute of Medical Research, Wellington 6242, New Zealand [2] School of Biological Sciences, Victoria University of Wellington, Wellington 6012, New Zealand.
Ryan
R
Kyle
Malaghan Institute of Medical Research, Wellington 6242, New Zealand.
Mali
M
Camberis
Malaghan Institute of Medical Research, Wellington 6242, New Zealand.
Amy
A
Shepherd
Malaghan Institute of Medical Research, Wellington 6242, New Zealand.
Kara
K
Filbey
Malaghan Institute of Medical Research, Wellington 6242, New Zealand.
Alexander
0000000345933042
A
Smith
Queensland University of Technology, Brisbane, Queensland 4000, Australia.
Marina
M
Harvie
The Ferrier Research Institute, Victoria University of Wellington, Lower Hutt, Wellington 5010, New Zealand.
Gavin
G
Painter
The Ferrier Research Institute, Victoria University of Wellington, Lower Hutt, Wellington 5010, New Zealand.
Karen
K
Johnston
Department of Pathology and Molecular Medicine, University of Otago, Wellington 6242, New Zealand.
Peter
P
Ferguson
1] The Centenary Institute, Sydney, New South Wales 2050, Australia [2] Discipline of Dermatology, Sydney Medical School, Sydney, New South Wales 2052, Australia.
Rohit
000000024905462X
R
Jain
1] The Centenary Institute, Sydney, New South Wales 2050, Australia [2] Discipline of Dermatology, Sydney Medical School, Sydney, New South Wales 2052, Australia.
Ben
B
Roediger
Department of Pathology and Molecular Medicine, University of Otago, Wellington 6242, New Zealand.
Brett
B
Delahunt
1] The Centenary Institute, Sydney, New South Wales 2050, Australia [2] Discipline of Dermatology, Sydney Medical School, Sydney, New South Wales 2052, Australia [3] Department of Dermatology, Royal Prince Alfred Hospital, Camperdown, New South Wales 2050, Australia.
Wolfgang
W
Weninger
Malaghan Institute of Medical Research, Wellington 6242, New Zealand.
Elizabeth
E
Forbes-Blom
Malaghan Institute of Medical Research, Wellington 6242, New Zealand.
Graham
G
Le Gros
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D054884:Host-Pathogen Interactions / Q000276:immunology*; D007376:Interleukin-2 / Q000378:metabolism; D000067596:Interleukin-33 / Q000378:metabolism; D008168:Lung / Q000276:immunology*; D008264:Macrophages / Q000502:physiology*; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000502:physiology; D009559:Nippostrongylus / Q000502:physiology*; D011917:Rats, Inbred Lew
C506535:Il33 protein, mouse; D007376:Interleukin-2; D000067596:Interleukin-33