RGD Reference Report - Impaired Recognition of Mycobacterium tuberculosis by Alveolar Macrophages From Diabetic Mice. - Rat Genome Database

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Impaired Recognition of Mycobacterium tuberculosis by Alveolar Macrophages From Diabetic Mice.

Authors: Martinez, Nuria  Ketheesan, Natkunam  West, Kim  Vallerskog, Therese  Kornfeld, Hardy 
Citation: Martinez N, etal., J Infect Dis. 2016 Dec 1;214(11):1629-1637. doi: 10.1093/infdis/jiw436. Epub 2016 Sep 13.
RGD ID: 41412199
Pubmed: PMID:27630197   (View Abstract at PubMed)
PMCID: PMC5144731   (View Article at PubMed Central)
DOI: DOI:10.1093/infdis/jiw436   (Journal Full-text)


BACKGROUND:  Diabetes mellitus is associated with increased tuberculosis risk and severity. We previously reported that tuberculosis susceptibility in diabetic mice results from a delay in innate immune response to inhaled Mycobacterium tuberculosis, leading to delayed adaptive immune priming and, consequently, a higher plateau lung bacterial burden and greater immune pathology.
METHODS:  We tested the capacity of alveolar macrophages from diabetic mice to phagocytose M. tuberculosis ex vivo and promote T-cell activation in vivo.
RESULTS:  Alveolar macrophages from diabetic mice had reduced expression of CD14 and macrophage receptor with collagenous structure (MARCO), which recognize the bacterial cell wall component trehalose 6,6'-dimycolate (TDM). Diabetic alveolar macrophages exhibited reduced phagocytosis of M. tuberculosis or TDM-coated latex beads. This alveolar macrophage phenotype was absent in peritoneal and bone marrow-derived macrophages. Transfer of infected alveolar macrophages from diabetic mice into nondiabetic recipients confirmed an intrinsic alveolar macrophage defect that hindered T-cell priming. The diabetic alveolar macrophage phenotype depended in part on expression of the receptor for advanced glycation end products.
CONCLUSIONS:  Reduced MARCO and CD14 expression contributes to defective sentinel function of alveolar macrophages, promoting tuberculosis susceptibility in diabetic hosts at a critical early step in the immune response to aerosol infection.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MARCOHumandiabetes mellitus  ISOMarco (Mus musculus)protein:decreased expression:Alveolar macrophageRGD 
MarcoMousediabetes mellitus  IEP protein:decreased expression:Alveolar macrophageRGD 
MarcoRatdiabetes mellitus  ISOMarco (Mus musculus)protein:decreased expression:Alveolar macrophageRGD 

Objects Annotated

Genes (Rattus norvegicus)
Marco  (macrophage receptor with collagenous structure)

Genes (Mus musculus)
Marco  (macrophage receptor with collagenous structure)

Genes (Homo sapiens)
MARCO  (macrophage receptor with collagenous structure)


Additional Information