title: Monocyte-derived macrophages do not explain susceptibility to pulmonary non-tuberculous mycobacterial disease.
abstract: Pulmonary infections with non-tuberculous mycobacteria (NTM) affect a subset of older individuals (mostly women) with no known immunological defects. As NTMs are intracellular pathogens, it is important to establish whether NTM disease is associated with defective production of Th1 cytokines or poor responses by host macrophage/monocytes. We have shown that patients display vigorous production of interferon gamma (IFNγ) when CD4 T cells are stimulated with mycobacterial antigens. This implicated the macrophage response to IFNγ. Blood monocytes are poorly representative of lung macrophages, so monocyte-derived macrophages (MDMs) were created and then stimulated with lipomannan (a Toll-like receptor (TLR)2 agonist), lipopolysaccharide (LPS; a TLR4 agonist) or recombinant human IFNγ. MDMs from NTM patients, their offspring and healthy donors expressed similar amounts of IFNγR1, and cellular responses to IFNγ were similar, so there is no evidence of a genetic defect in this pathway. MDMs from NTM patients produced less interleukin-6 in response to LPS (P<0.01) than cells from controls, but other cytokine responses were normal. This warrants further study.
authors.affiliation: School of Pathology and Laboratory Medicine, University of Western Australia , Nedlands, WA, Australia.
authors.forename: Emma
authors.initials: E
authors.lastname: de Jong
authors.affiliation: School of Pathology and Laboratory Medicine, University of Western Australia , Nedlands, WA, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Lim
authors.affiliation: School of Medicine and Pharmacology, University of Western Australia , Nedlands, WA, Australia.
authors.forename: Grant
authors.initials: G
authors.lastname: Waterer
authors.affiliation: School of Pathology and Laboratory Medicine, University of Western Australia , Nedlands, WA, Australia.
authors.forename: Patricia
authors.initials: P
authors.lastname: Price
keywords: Toll-like receptors; interferon gamma; macrophages; monocytes; non-tuberculous mycobacteria