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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

TLR2 and IL-6 responses are lower in NTM patients. TLR2 (a), TNFα (b), IL-10 (c) and IL-6 (d) responses assessed in MDMs from NTM patients (●), their offspring (○) and healthy population controls (⧫), with and without bacterial stimulation over 24 h. Horizontal lines represent median values. *P=0.05–0.01, patients versus offspring and population controls combined. **P<0.01, patients versus offspring and population controls combined (a) or patients versus population controls (d).
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fig1: TLR2 and IL-6 responses are lower in NTM patients. TLR2 (a), TNFα (b), IL-10 (c) and IL-6 (d) responses assessed in MDMs from NTM patients (●), their offspring (○) and healthy population controls (⧫), with and without bacterial stimulation over 24 h. Horizontal lines represent median values. *P=0.05–0.01, patients versus offspring and population controls combined. **P<0.01, patients versus offspring and population controls combined (a) or patients versus population controls (d).

Mentions: MDMs were cultured for 24 h with or without LM or LPS. Expression of TLR2 was assessed by flow cytometry, and levels of TNFα, IL-6 and IL-10 were assessed in supernatants. Compared with unstimulated cells, MDMs from all donors expressed more TLR2 after stimulation with LM or LPS (P=0.0006–0.024, Kruskal–Wallis test). The median level of TLR2 was marginally lower in NTM patients (Figure 1a). This difference became significant (P<0.05 and P<0.01 for LM and LPS, respectively) when MDMs from NTM patients were compared with MDMs from all healthy donors (offspring and healthy controls pooled).


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)

TLR2 and IL-6 responses are lower in NTM patients. TLR2 (a), TNFα (b), IL-10 (c) and IL-6 (d) responses assessed in MDMs from NTM patients (●), their offspring (○) and healthy population controls (⧫), with and without bacterial stimulation over 24 h. Horizontal lines represent median values. *P=0.05–0.01, patients versus offspring and population controls combined. **P<0.01, patients versus offspring and population controls combined (a) or patients versus population controls (d).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: TLR2 and IL-6 responses are lower in NTM patients. TLR2 (a), TNFα (b), IL-10 (c) and IL-6 (d) responses assessed in MDMs from NTM patients (●), their offspring (○) and healthy population controls (⧫), with and without bacterial stimulation over 24 h. Horizontal lines represent median values. *P=0.05–0.01, patients versus offspring and population controls combined. **P<0.01, patients versus offspring and population controls combined (a) or patients versus population controls (d).
Mentions: MDMs were cultured for 24 h with or without LM or LPS. Expression of TLR2 was assessed by flow cytometry, and levels of TNFα, IL-6 and IL-10 were assessed in supernatants. Compared with unstimulated cells, MDMs from all donors expressed more TLR2 after stimulation with LM or LPS (P=0.0006–0.024, Kruskal–Wallis test). The median level of TLR2 was marginally lower in NTM patients (Figure 1a). This difference became significant (P<0.05 and P<0.01 for LM and LPS, respectively) when MDMs from NTM patients were compared with MDMs from all healthy donors (offspring and healthy controls pooled).

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