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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

MDMs from NTM patients exhibit a normal capacity for phagocytosis. The proportions of phagocytic MDMs (FITC+ cells) determined by co-culture with rabbit IgG FITC-conjugated latex beads for 2 h was similar between healthy controls (n=6), offspring (n=3) and NTM patients (n=12). Horizontal lines represent median values.
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fig4: MDMs from NTM patients exhibit a normal capacity for phagocytosis. The proportions of phagocytic MDMs (FITC+ cells) determined by co-culture with rabbit IgG FITC-conjugated latex beads for 2 h was similar between healthy controls (n=6), offspring (n=3) and NTM patients (n=12). Horizontal lines represent median values.

Mentions: To determine whether an impairment in phagocytosis was associated with NTM disease, MDMs from healthy controls, offspring and patients were cultured for 2 h with rabbit IgG fluorescein isothiocyanate (FITC)-conjugated latex beads. There was no significant difference in the phagocytic capacities of MDMs across subject groups (Figure 4). Intracellular levels of COX-1, COX-2 and inducible nitric oxide synthase were measured by flow cytometry following stimulation with LM or LPS. Levels were not deficient in MDMs from NTM patients, compared with offspring or healthy controls (data not shown).


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)

MDMs from NTM patients exhibit a normal capacity for phagocytosis. The proportions of phagocytic MDMs (FITC+ cells) determined by co-culture with rabbit IgG FITC-conjugated latex beads for 2 h was similar between healthy controls (n=6), offspring (n=3) and NTM patients (n=12). Horizontal lines represent median values.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig4: MDMs from NTM patients exhibit a normal capacity for phagocytosis. The proportions of phagocytic MDMs (FITC+ cells) determined by co-culture with rabbit IgG FITC-conjugated latex beads for 2 h was similar between healthy controls (n=6), offspring (n=3) and NTM patients (n=12). Horizontal lines represent median values.
Mentions: To determine whether an impairment in phagocytosis was associated with NTM disease, MDMs from healthy controls, offspring and patients were cultured for 2 h with rabbit IgG fluorescein isothiocyanate (FITC)-conjugated latex beads. There was no significant difference in the phagocytic capacities of MDMs across subject groups (Figure 4). Intracellular levels of COX-1, COX-2 and inducible nitric oxide synthase were measured by flow cytometry following stimulation with LM or LPS. Levels were not deficient in MDMs from NTM patients, compared with offspring or healthy controls (data not shown).

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