1 The Centenary Institute
1 The Centenary Institute
PubMed | University of New South Wales, The Centenary Institute, Monash University, Harvard University and 2 more.
Type: Journal Article | Journal: Nature immunology | Year: 2013
Transendothelial migration of neutrophils in postcapillary venules is a key event in the inflammatory response against pathogens and tissue damage. The precise regulation of this process is incompletely understood. We report that perivascular macrophages are critical for neutrophil migration into skin infected with the pathogen Staphylococcus aureus. Using multiphoton intravital microscopy we showed that neutrophils extravasate from inflamed dermal venules in close proximity to perivascular macrophages, which are a major source of neutrophil chemoattractants. The virulence factor -hemolysin produced by S. aureus lyses perivascular macrophages, which leads to decreased neutrophil transmigration. Our data illustrate a previously unrecognized role for perivascular macrophages in neutrophil recruitment to inflamed skin and indicate that S. aureus uses hemolysin-dependent killing of these cells as an immune evasion strategy.
PubMed | University of Otago, Victoria University of Wellington, Malaghan Institute of Medical Research, Queensland University of Technology and 1 The Centenary Institute
Type: | Journal: Nature communications | Year: 2015
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 48h 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 ILC2s 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.
PubMed | 1 The Centenary Institute
Type: Journal Article | Journal: Immunology and cell biology | Year: 2015
The skin serves as a critical barrier against pathogen entry. This protection is afforded by an array of skin-resident immune cells, which act as first-line responders against barrier breach and infection. The recruitment and positioning of these cells is controlled at multiple levels by endothelial cells, pericytes, perivascular macrophages and mast cells, and by the fibroblasts in the dermis and keratinocytes in the epidermis. Chemokine signalling through chemokine receptors expressed by the various leukocyte subsets is critical for their trafficking into and within the skin. The role of chemokines in the skin is complex, and remains incompletely understood despite three decades of investigation. Here, we review the roles that different chemokine pathways play in the skin, and highlight the recent developments in the field.