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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

NTM disease is not associated with reduced responses by blood monocytes. Expression of TLR2 and TLR4 on unstimulated monocytes (a), and percentages of monocytes expressing IL-6 (b) and TNFα (c) after 6 h stimulation. Horizontal lines represent median values.
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fig3: NTM disease is not associated with reduced responses by blood monocytes. Expression of TLR2 and TLR4 on unstimulated monocytes (a), and percentages of monocytes expressing IL-6 (b) and TNFα (c) after 6 h stimulation. Horizontal lines represent median values.

Mentions: Uncultured peripheral blood mononuclear cells (PBMCs) from a subset of donors (n=10–12) were used to assess expression of TLR2 and TLR4 on CD14+ monocytes. PBMCs were then stimulated for 6 h with LPS or LM to assess production of IL-6 and TNFα. Monocytes from patients and controls did not differ significantly in their expression of TLR2 or TLR4 (Figure 3a), or in production of IL-6 or TNFα (Figures 3b and c). Although the median level of IL-6 production may be slightly lower in NTM patients in response to LPS, the trend did not reach statistical significance (P=0.118; Mann–Whitney's test).


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)

NTM disease is not associated with reduced responses by blood monocytes. Expression of TLR2 and TLR4 on unstimulated monocytes (a), and percentages of monocytes expressing IL-6 (b) and TNFα (c) after 6 h stimulation. Horizontal lines represent median values.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig3: NTM disease is not associated with reduced responses by blood monocytes. Expression of TLR2 and TLR4 on unstimulated monocytes (a), and percentages of monocytes expressing IL-6 (b) and TNFα (c) after 6 h stimulation. Horizontal lines represent median values.
Mentions: Uncultured peripheral blood mononuclear cells (PBMCs) from a subset of donors (n=10–12) were used to assess expression of TLR2 and TLR4 on CD14+ monocytes. PBMCs were then stimulated for 6 h with LPS or LM to assess production of IL-6 and TNFα. Monocytes from patients and controls did not differ significantly in their expression of TLR2 or TLR4 (Figure 3a), or in production of IL-6 or TNFα (Figures 3b and c). Although the median level of IL-6 production may be slightly lower in NTM patients in response to LPS, the trend did not reach statistical significance (P=0.118; Mann–Whitney's test).

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