Giuseppe
Emeritus
[Source: PLoS ONE, full text: (LINK). Abstract, edited.]
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Influenza-Infected Neutrophils within the Infected Lungs Act as Antigen Presenting Cells for Anti-Viral CD8<SUP>+</SUP> T Cells
Matthew M. Hufford<SUP>1</SUP><SUP>,</SUP><SUP>2</SUP><SUP>#</SUP>, Graham Richardson<SUP>2</SUP><SUP>,</SUP><SUP>3</SUP><SUP>#</SUP>, Haixia Zhou<SUP>1</SUP>, Balaji Manicassamy<SUP>4</SUP><SUP>,</SUP><SUP>5</SUP>, Adolfo Garc?a-Sastre<SUP>4</SUP><SUP>,</SUP><SUP>5</SUP><SUP>,</SUP><SUP>6</SUP>, Richard I. Enelow<SUP>7</SUP>, Thomas J. Braciale<SUP>1</SUP><SUP>,</SUP><SUP>2</SUP><SUP>,</SUP><SUP>8</SUP><SUP>*</SUP>
<SUP></SUP>
1 The Beirne B. Carter Center for Immunology Research, The University of Virginia, Charlottesville, Virginia, United States of America, 2 Department of Microbiology, The University of Virginia, Charlottesville, Virginia, United States of America, 3 Center for Cell Signaling, The University of Virginia, Charlottesville, Virginia, United States of America, 4 Department of Microbiology, Mount Sinai School of Medicine, New York City, New York, United States of America, 5 Global Health and Emerging Pathogens Institute, Mount Sinai School of Medicine, New York City, New York, United States of America, 6 Department of Medicine, Division of Infectious Diseases, Mount Sinai School of Medicine, New York City, New York, United States of America, 7 Departments of Medicine and Microbiology/Immunology, Dartmouth Medical School, Lebanon, New Hampshire, United States of America, 8 Department of Pathology, The University of Virginia, Charlottesville, Virginia, United States of America
Abstract
Influenza A virus (IAV) is a leading cause of respiratory tract disease worldwide. Anti-viral CD8<SUP>+</SUP> T lymphocytes responding to IAV infection are believed to eliminate virally infected cells by direct cytolysis but may also contribute to pulmonary inflammation and tissue damage via the release of pro-inflammatory mediators following recognition of viral antigen displaying cells. We have previously demonstrated that IAV antigen expressing inflammatory cells of hematopoietic origin within the infected lung interstitium serve as antigen presenting cells (APC) for infiltrating effector CD8<SUP>+</SUP> T lymphocytes; however, the spectrum of inflammatory cell types capable of serving as APC was not determined. Here, we demonstrate that viral antigen displaying neutrophils infiltrating the IAV infected lungs are an important cell type capable of acting as APC for effector CD8<SUP>+</SUP> T lymphocytes in the infected lungs and that neutrophils expressing viral antigen as a result of direct infection by IAV exhibit the most potent APC activity. Our findings suggest that in addition to their suggested role in induction of the innate immune responses to IAV, virus clearance, and the development of pulmonary injury, neutrophils can serve as APCs to anti-viral effector CD8<SUP>+</SUP> T cells within the infected lung interstitium.
Citation: Hufford MM, Richardson G, Zhou H, Manicassamy B, Garc?a-Sastre A, et al. (2012) Influenza-Infected Neutrophils within the Infected Lungs Act as Antigen Presenting Cells for Anti-Viral CD8<SUP>+</SUP> T Cells. PLoS ONE 7(10): e46581. doi:10.1371/journal.pone.0046581
Editor: Steven M. Varga, University of Iowa, United States of America
Received: July 4, 2012; Accepted: August 31, 2012; Published: October 8, 2012
Copyright: ? 2012 Hufford et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: These studies were supported by grants from the National Institutes of Health (NIH) to TJB (RO1 AI-15608, RO1 AI-37293, RO1 HL-33391, and U-10 AI-83024), to RIE (U-19 AI-83024), to the Mucosal Immunity Study Team Program and AGS (U19 AI-083025 and U01 AI-095611), to BM (NIH K99 Pathway to Independence Award 1K99 AI095320-01), and to MMH (T32 AI007496-13). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: tjb2r@virginia.edu
# These authors contributed equally to this work.
-Matthew M. Hufford<SUP>1</SUP><SUP>,</SUP><SUP>2</SUP><SUP>#</SUP>, Graham Richardson<SUP>2</SUP><SUP>,</SUP><SUP>3</SUP><SUP>#</SUP>, Haixia Zhou<SUP>1</SUP>, Balaji Manicassamy<SUP>4</SUP><SUP>,</SUP><SUP>5</SUP>, Adolfo Garc?a-Sastre<SUP>4</SUP><SUP>,</SUP><SUP>5</SUP><SUP>,</SUP><SUP>6</SUP>, Richard I. Enelow<SUP>7</SUP>, Thomas J. Braciale<SUP>1</SUP><SUP>,</SUP><SUP>2</SUP><SUP>,</SUP><SUP>8</SUP><SUP>*</SUP>
<SUP></SUP>
1 The Beirne B. Carter Center for Immunology Research, The University of Virginia, Charlottesville, Virginia, United States of America, 2 Department of Microbiology, The University of Virginia, Charlottesville, Virginia, United States of America, 3 Center for Cell Signaling, The University of Virginia, Charlottesville, Virginia, United States of America, 4 Department of Microbiology, Mount Sinai School of Medicine, New York City, New York, United States of America, 5 Global Health and Emerging Pathogens Institute, Mount Sinai School of Medicine, New York City, New York, United States of America, 6 Department of Medicine, Division of Infectious Diseases, Mount Sinai School of Medicine, New York City, New York, United States of America, 7 Departments of Medicine and Microbiology/Immunology, Dartmouth Medical School, Lebanon, New Hampshire, United States of America, 8 Department of Pathology, The University of Virginia, Charlottesville, Virginia, United States of America
Abstract
Influenza A virus (IAV) is a leading cause of respiratory tract disease worldwide. Anti-viral CD8<SUP>+</SUP> T lymphocytes responding to IAV infection are believed to eliminate virally infected cells by direct cytolysis but may also contribute to pulmonary inflammation and tissue damage via the release of pro-inflammatory mediators following recognition of viral antigen displaying cells. We have previously demonstrated that IAV antigen expressing inflammatory cells of hematopoietic origin within the infected lung interstitium serve as antigen presenting cells (APC) for infiltrating effector CD8<SUP>+</SUP> T lymphocytes; however, the spectrum of inflammatory cell types capable of serving as APC was not determined. Here, we demonstrate that viral antigen displaying neutrophils infiltrating the IAV infected lungs are an important cell type capable of acting as APC for effector CD8<SUP>+</SUP> T lymphocytes in the infected lungs and that neutrophils expressing viral antigen as a result of direct infection by IAV exhibit the most potent APC activity. Our findings suggest that in addition to their suggested role in induction of the innate immune responses to IAV, virus clearance, and the development of pulmonary injury, neutrophils can serve as APCs to anti-viral effector CD8<SUP>+</SUP> T cells within the infected lung interstitium.
Citation: Hufford MM, Richardson G, Zhou H, Manicassamy B, Garc?a-Sastre A, et al. (2012) Influenza-Infected Neutrophils within the Infected Lungs Act as Antigen Presenting Cells for Anti-Viral CD8<SUP>+</SUP> T Cells. PLoS ONE 7(10): e46581. doi:10.1371/journal.pone.0046581
Editor: Steven M. Varga, University of Iowa, United States of America
Received: July 4, 2012; Accepted: August 31, 2012; Published: October 8, 2012
Copyright: ? 2012 Hufford et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: These studies were supported by grants from the National Institutes of Health (NIH) to TJB (RO1 AI-15608, RO1 AI-37293, RO1 HL-33391, and U-10 AI-83024), to RIE (U-19 AI-83024), to the Mucosal Immunity Study Team Program and AGS (U19 AI-083025 and U01 AI-095611), to BM (NIH K99 Pathway to Independence Award 1K99 AI095320-01), and to MMH (T32 AI007496-13). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: tjb2r@virginia.edu
# These authors contributed equally to this work.
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