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Wellington, New Zealand

Prendergast K.A.,Malaghan Institute of Medical Research | Kirman J.R.,University of Otago

Anti-mycobacterial immunity is guided by specialised antigen presenting cells known as dendritic cells, which are essential for both initiating and maintaining T cell immune responses during infection. The dendritic cell population can be divided into functionally distinct subsets that differ in their ability to present antigen and produce key TH1 cytokines, such as IL-12. This review discusses recent studies, in murine models, investigating which dendritic cell populations are important for mycobacterial control. © 2012 Elsevier Ltd. All rights reserved. Source

Hunn M.K.,Malaghan Institute of Medical Research | Hermans I.F.,Victoria University of Wellington

Invariant natural killer T (iNKT) cells have the capacity to amplify adaptive immune responses by licensing antigenpresenting cells. A simple vaccine consisting of whole tumor cells pulsed with an iNKT-cell agonist efficiently delivers antigens plus adjuvants to endogenous dendritic cells and has potential for clinical applications. © 2013 Landes Bioscience. Source

Harvie M.,Queensland University of Technology | Camberis M.,Malaghan Institute of Medical Research | Gros G.L.,Malaghan Institute of Medical Research
Frontiers in Immunology

Of all the microbial infections relevant to mammals the relationship between parasitic worms and what constitutes and regulates a host protective immune response is perhaps the most complex and evolved. Nippostrongylus brasiliensis is a tissue migrating parasitic roundworm of rodents that exemplifies many of the salient features of parasitic worm infection, including parasite development through sequential larval stages as it migrates through specific tissue sites. Immune competent hosts respond to infection by N. brasiliensis with a rapid and selective development of a profound Th2 immune response that appears able to confer life long protective immunity against reinfection. This review details how the lung can be the site of migrating nematode immune killing and the gut a site of rapid immune mediated clearance of worms. Furthermore it appears that N. brasiliensis induced responses in the lung are sufficient for conferring immunity in lung and gut while infection of the gut only confers immunity in the gut. This review also covers the role of IL-4, STAT6, and the innate cytokines IL-25, IL-33, and thymic stromal lymphopoietin in the generation of CD4-mediated immunity against N. brasiliensis reinfection and discusses what cytokines might be involved in mediated killing or expulsion of helminth parasites. © 2013 Harvie, Camberis and Le Gros. Source

Objective To identify macrophage-independent sources of transforming growth factor β1 (TGFβ1) production during monosodium urate monohydrate (MSU) crystal-induced inflammation and to determine how TGFβ1 alters MSU crystal-recruited neutrophil functions. Methods C57BL/6J mice were injected intraperitoneally with MSU crystals with or without TGFβ1-neutralizing antibody. MSU crystal-recruited peritoneal and blood neutrophils were purified and cultured ex vivo. Peritoneal neutrophils were treated with the caspase inhibitor Q-VD-OPh, anti-TGFβ1 antibody, or fluorochrome-labeled apoptotic neutrophils. Neutrophils were analyzed for expression of annexin V, caspase 3, and TGFβ1 by flow cytometry or fluorescence microscopy, for superoxide production using the redox-sensitive dye water-soluble tetrazolium 1, and for TGFβ1 and interleukin-1β (IL-1β) production by enzyme-linked immunosorbent assay. Results Eighteen hours after MSU crystal administration in vivo, TGFβ1 levels were elevated in peritoneal lavage fluids, and a significant number of peritoneal neutrophils were TGFβ1+. Purified blood or peritoneal neutrophils cultured ex vivo showed TGFβ1+ neutrophils coexpressing the apoptosis marker caspase 3 and increased TGFβ1 production, both of which dropped following inhibition of apoptosis. Live neutrophils that had phagocytosed apoptotic neutrophils showed greatest TGFβ1 expression. Superoxide production by purified MSU crystal-recruited neutrophils ex vivo was enhanced by anti-TGFβ1 antibody treatment. Neutrophils purified from the peritoneum of MSU crystal-challenged mice treated with anti-TGFβ1 antibody produced elevated levels of superoxide, but neutrophil IL-1β production was unaffected. Conclusion Neutrophil cannibalism and TGFβ1 production have the potential to make a significant contribution to the controlled resolution of neutrophil-driven inflammatory diseases such as gout. © 2013 by the American College of Rheumatology. Source

Martin W.J.,Malaghan Institute of Medical Research | Harper J.L.,Malaghan Institute of Medical Research
Immunology and Cell Biology

Acute gout is an inflammatory arthritis that is controlled by the innate arm of the immune response. Although the causative feature of gout has long been recognized, it is surprising that the cellular activities that underpin the initiation and resolution of acute gout remain poorly described. This review article summarizes what are currently thought to be the key cellular mechanisms at play during an inflammatory episode of acute gout. The emerging role of mononuclear phagocytes is highlighted as having a central role in both the initiation and resolution of acute gout, and the interplay between monocytes and other elements of the innate immune response, including neutrophils, and complement protein activation are discussed. © 2010 Australasian Society for Immunology Inc. All rights reserved. Source

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