Distinct responses of human monocyte subsets to Aspergillus fumigatus conidia Journal Article

Authors: Serbina, N. V.; Cherny, M.; Shi, C.; Bleau, S. A.; Collins, N. H.; Young, J. W.; Pamer, E. G.
Article Title: Distinct responses of human monocyte subsets to Aspergillus fumigatus conidia
Abstract: Aspergillus fumigatus is an environmental fungus that causes life-threatening infections in neutropenic patients. In the absence of intact innate immunity, inhaled A. fumigatus spores (conidia) germinate in the lung, forming hyphae that invade blood vessels and disseminate to other tissues. Although macrophages and neutrophils are postulated to provide defense against invasive fungal infection, animal models and human studies suggest that circulating monocytes also contribute to antifungal immunity. Although human monocyte subsets, defined as either CD14<sup>+</sup>CD16<sup>-</sup> or CD14<sup>+</sup>CD16<sup>+</sup>, have been extensively characterized, their respective roles during fungal infection remain undefined. We isolated CD14 <sup>+</sup>CD16<sup>-</sup> and CD14<sup>+</sup>CD16<sup>+</sup> monocytes from healthy allogeneic hematopoietic stem cell transplantation donors and compared their ability to phagocytose and inhibit A. fumigatus conidia. Both monocyte subsets efficiently phagocytose conidia, but only CD14<sup>+</sup>CD16 <sup>-</sup> monocytes inhibit conidial germination yet secrete little TNF. In contrast CD14<sup>+</sup>CD16<sup>+</sup> do not inhibit conidial germination and secrete large amounts of TNF. Although CD14<sup>+</sup>CD16<sup>-</sup> and CD14<sup>+</sup>CD16<sup>+</sup> monocytes differ in their response to dormant conidia, responses are similar if conidia are already germinated at the time of monocyte uptake. Our study demonstrates that functional CD14 <sup>+</sup>CD16<sup>-</sup> and CD14<sup>+</sup>CD16<sup>+</sup> monocytes can be isolated from allogeneic hematopoietic stem cell transplantation donors and that these subsets differ in their response to A. fumigatus conidia. Copyright © 2009 by The American Association of Immunologists, Inc.
Keywords: controlled study; cytology; metabolism; cell viability; cells, cultured; cd34 antigen; interleukin 10; down-regulation; hematopoietic stem cell transplantation; growth, development and aging; cd16 antigen; biosynthesis; immunology; immune response; tumor necrosis factor alpha; cell culture; stem cell mobilization; allogeneic hematopoietic stem cell transplantation; fc receptor; receptors, igg; down regulation; upregulation; monocyte; monocytes; up-regulation; microbiology; phagocytosis; cytokine release; granulocyte colony stimulating factor; granulocyte colony-stimulating factor; antigens, cd34; hematopoietic stem cell mobilization; aspergillus fumigatus; conidium; aspergillosis; fungus spore; interleukin 12; cd14 antigen; fungus growth; germination; interleukin 1; antigens, cd14; spores, fungal
Journal Title: Journal of Immunology
Volume: 183
Issue: 4
ISSN: 0022-1767
Publisher: The American Association of Immunologists, Inc  
Date Published: 2009-08-15
Start Page: 2678
End Page: 2687
Language: English
DOI: 10.4049/jimmunol.0803398
PUBMED: 19635902
PROVIDER: scopus
PMCID: PMC2753882
Notes: --- - "Cited By (since 1996): 3" - "Export Date: 30 November 2010" - "CODEN: JOIMA" - "Source: Scopus"
Citation Impact
MSK Authors
  1. Eric Pamer
    277 Pamer
  2. James W Young
    300 Young
  3. Natalya Serbina
    17 Serbina
  4. Nancy Collins
    86 Collins
  5. Chao Shi
    14 Shi
  6. Mathew Aaron Cherny
    2 Cherny
  7. Sharon A Bleau
    16 Bleau