RGD Reference Report - Scavenger Receptor MARCO Orchestrates Early Defenses and Contributes to Fungal Containment during Cryptococcal Infection. - Rat Genome Database

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Scavenger Receptor MARCO Orchestrates Early Defenses and Contributes to Fungal Containment during Cryptococcal Infection.

Authors: Xu, Jintao  Flaczyk, Adam  Neal, Lori M  Fa, Zhenzong  Eastman, Alison J  Malachowski, Antoni N  Cheng, Daphne  Moore, Bethany B  Curtis, Jeffrey L  Osterholzer, John J  Olszewski, Michal A 
Citation: Xu J, etal., J Immunol. 2017 May 1;198(9):3548-3557. doi: 10.4049/jimmunol.1700057. Epub 2017 Mar 15.
RGD ID: 41412191
Pubmed: PMID:28298522   (View Abstract at PubMed)
PMCID: PMC5423401   (View Article at PubMed Central)
DOI: DOI:10.4049/jimmunol.1700057   (Journal Full-text)

The scavenger receptor macrophage receptor with collagenous structure (MARCO) promotes protective innate immunity against bacterial and parasitic infections; however, its role in host immunity against fungal pathogens, including the major human opportunistic fungal pathogen Cryptococcus neoformans, remains unknown. Using a mouse model of C. neoformans infection, we demonstrated that MARCO deficiency leads to impaired fungal control during the afferent phase of cryptococcal infection. Diminished fungal containment in MARCO-/- mice was accompanied by impaired recruitment of Ly6Chigh monocytes and monocyte-derived dendritic cells (moDC) and lower moDC costimulatory maturation. The reduced recruitment and activation of mononuclear phagocytes in MARCO-/- mice was linked to diminished early expression of IFN-γ along with profound suppression of CCL2 and CCL7 chemokines, providing evidence for roles of MARCO in activation of the CCR2 axis during C. neoformans infection. Lastly, we found that MARCO was involved in C. neoformans phagocytosis by resident pulmonary macrophages and DC. We conclude that MARCO facilitates early interactions between C. neoformans and lung-resident cells and promotes the production of CCR2 ligands. In turn, this contributes to a more robust recruitment and activation of moDC that opposes rapid fungal expansion during the afferent phase of cryptococcal infection.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MARCOHumanBacterial Lung Diseases disease_progressionISOMarco (Mus musculus)association with Cryptococcal neoformans infection.RGD 
MarcoMouseBacterial Lung Diseases disease_progressionIMP association with Cryptococcal neoformans infection.RGD 
MarcoRatBacterial Lung Diseases disease_progressionISOMarco (Mus musculus)association with Cryptococcal neoformans infection.RGD 
MARCOHumancryptococcosis disease_progressionISOMarco (Mus musculus) RGD 
MarcoMousecryptococcosis disease_progressionIMP  RGD 
MarcoRatcryptococcosis disease_progressionISOMarco (Mus musculus) RGD 

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