Limits...
Monocyte-derived macrophages do not explain susceptibility to pulmonary non-tuberculous mycobacterial disease.

de Jong E, Lim A, Waterer G, Price P - Clin Transl Immunology (2012)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: School of Pathology and Laboratory Medicine, University of Western Australia , Nedlands, WA, Australia.

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.

No MeSH data available.


Related in: MedlinePlus

Macrophages from NTM patients display normal expression of IFNγR1 and CXC10 responses to IFNγ. Levels of CXCL10 (a) and expression of IFNγR1 (b) in MDM cultures after 24 h stimulation with rhIFNγ. Horizontal lines represent median values.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4256549&req=5

fig2: Macrophages from NTM patients display normal expression of IFNγR1 and CXC10 responses to IFNγ. Levels of CXCL10 (a) and expression of IFNγR1 (b) in MDM cultures after 24 h stimulation with rhIFNγ. Horizontal lines represent median values.

Mentions: MDMs were cultured for 24 h in the presence of media alone or two concentrations of rhIFNγ, and CXCL10 was measured by enzyme-linked immunosorbent assay. Macrophages from NTM patients, offspring and controls produced similar levels of CXCL10 across all culture conditions (P=0.057–0.49; Figure 2a). Stimulation of MDMs with 10 ng ml−1 rhIFNγ reduced expression of IFNγR1 in cells from NTM patients (Wilcoxon's matched pair test, P<0.0001), offspring (P=0.0024) and healthy controls (P=0.0029), but created no differences between groups (P=0.65–0.94; Figure 2b).


Monocyte-derived macrophages do not explain susceptibility to pulmonary non-tuberculous mycobacterial disease.

de Jong E, Lim A, Waterer G, Price P - Clin Transl Immunology (2012)

Macrophages from NTM patients display normal expression of IFNγR1 and CXC10 responses to IFNγ. Levels of CXCL10 (a) and expression of IFNγR1 (b) in MDM cultures after 24 h stimulation with rhIFNγ. Horizontal lines represent median values.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4256549&req=5

fig2: Macrophages from NTM patients display normal expression of IFNγR1 and CXC10 responses to IFNγ. Levels of CXCL10 (a) and expression of IFNγR1 (b) in MDM cultures after 24 h stimulation with rhIFNγ. Horizontal lines represent median values.
Mentions: MDMs were cultured for 24 h in the presence of media alone or two concentrations of rhIFNγ, and CXCL10 was measured by enzyme-linked immunosorbent assay. Macrophages from NTM patients, offspring and controls produced similar levels of CXCL10 across all culture conditions (P=0.057–0.49; Figure 2a). Stimulation of MDMs with 10 ng ml−1 rhIFNγ reduced expression of IFNγR1 in cells from NTM patients (Wilcoxon's matched pair test, P<0.0001), offspring (P=0.0024) and healthy controls (P=0.0029), but created no differences between groups (P=0.65–0.94; Figure 2b).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: School of Pathology and Laboratory Medicine, University of Western Australia , Nedlands, WA, Australia.

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.

No MeSH data available.


Related in: MedlinePlus