Exploitation of Scavenger Receptor, Macrophage Receptor with Collagenous Structure, by Cryptococcus neoformans Promotes Alternative Activation of Pulmonary Lymph Node CD11b+ Conventional Dendritic Cells and Non-Protective Th2 Bias
Macrophage receptor with collagenous structure (MARCO) contributes to fungal containment during the early/innate phase of cryptococcal infection; however, its role in adaptive antifungal immunity remains unknown. Using a murine model of cryptococcosis, we compared host adaptive immune responses in w...
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Format: | Article |
Language: | English |
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Frontiers Media S.A.
2017-09-01
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Series: | Frontiers in Immunology |
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Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2017.01231/full |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jintao Xu Jintao Xu Adam Flaczyk Lori M. Neal Lori M. Neal Zhenzong Fa Daphne Cheng Mike Ivey Bethany B. Moore Bethany B. Moore Jeffrey L. Curtis Jeffrey L. Curtis John J. Osterholzer John J. Osterholzer Michal A. Olszewski Michal A. Olszewski |
spellingShingle |
Jintao Xu Jintao Xu Adam Flaczyk Lori M. Neal Lori M. Neal Zhenzong Fa Daphne Cheng Mike Ivey Bethany B. Moore Bethany B. Moore Jeffrey L. Curtis Jeffrey L. Curtis John J. Osterholzer John J. Osterholzer Michal A. Olszewski Michal A. Olszewski Exploitation of Scavenger Receptor, Macrophage Receptor with Collagenous Structure, by Cryptococcus neoformans Promotes Alternative Activation of Pulmonary Lymph Node CD11b+ Conventional Dendritic Cells and Non-Protective Th2 Bias Frontiers in Immunology scavenger receptor macrophage receptor with collagenous structure fungal persistence Th2 response CD11b+ conventional DC Cryptococcus neoformans |
author_facet |
Jintao Xu Jintao Xu Adam Flaczyk Lori M. Neal Lori M. Neal Zhenzong Fa Daphne Cheng Mike Ivey Bethany B. Moore Bethany B. Moore Jeffrey L. Curtis Jeffrey L. Curtis John J. Osterholzer John J. Osterholzer Michal A. Olszewski Michal A. Olszewski |
author_sort |
Jintao Xu |
title |
Exploitation of Scavenger Receptor, Macrophage Receptor with Collagenous Structure, by Cryptococcus neoformans Promotes Alternative Activation of Pulmonary Lymph Node CD11b+ Conventional Dendritic Cells and Non-Protective Th2 Bias |
title_short |
Exploitation of Scavenger Receptor, Macrophage Receptor with Collagenous Structure, by Cryptococcus neoformans Promotes Alternative Activation of Pulmonary Lymph Node CD11b+ Conventional Dendritic Cells and Non-Protective Th2 Bias |
title_full |
Exploitation of Scavenger Receptor, Macrophage Receptor with Collagenous Structure, by Cryptococcus neoformans Promotes Alternative Activation of Pulmonary Lymph Node CD11b+ Conventional Dendritic Cells and Non-Protective Th2 Bias |
title_fullStr |
Exploitation of Scavenger Receptor, Macrophage Receptor with Collagenous Structure, by Cryptococcus neoformans Promotes Alternative Activation of Pulmonary Lymph Node CD11b+ Conventional Dendritic Cells and Non-Protective Th2 Bias |
title_full_unstemmed |
Exploitation of Scavenger Receptor, Macrophage Receptor with Collagenous Structure, by Cryptococcus neoformans Promotes Alternative Activation of Pulmonary Lymph Node CD11b+ Conventional Dendritic Cells and Non-Protective Th2 Bias |
title_sort |
exploitation of scavenger receptor, macrophage receptor with collagenous structure, by cryptococcus neoformans promotes alternative activation of pulmonary lymph node cd11b+ conventional dendritic cells and non-protective th2 bias |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2017-09-01 |
description |
Macrophage receptor with collagenous structure (MARCO) contributes to fungal containment during the early/innate phase of cryptococcal infection; however, its role in adaptive antifungal immunity remains unknown. Using a murine model of cryptococcosis, we compared host adaptive immune responses in wild-type and MARCO−/− mice throughout an extended time course post-infection. Unlike in early infection, MARCO deficiency resulted in improved pulmonary fungal clearance and diminished cryptococcal dissemination during the efferent phase. Improved fungal control in the absence of MARCO expression was associated with enhanced hallmarks of protective Th1-immunity, including higher frequency of pulmonary TNF-α-producing T cells, increased cryptococcal-antigen-triggered IFN-γ and TNF-α production by splenocytes, and enhanced expression of M1 polarization genes by pulmonary macrophages. Concurrently, we found lower frequencies of IL-5- and IL-13-producing T cells in the lungs, impaired production of IL-4 and IL-10 by cryptococcal antigen-pulsed splenocytes, and diminished serum IgE, which were hallmarks of profoundly suppressed efferent Th2 responses in MARCO-deficient mice compared to WT mice. Mechanistically, we found that MARCO expression facilitated early accumulation and alternative activation of CD11b+ conventional DC (cDC) in the lung-associated lymph nodes (LALNs), which contributed to the progressive shift of the immune response from Th1 toward Th2 at the priming site (LALNs) and local infection site (lungs) during the efferent phase of cryptococcal infection. Taken together, our study shows that MARCO can be exploited by the fungal pathogen to promote accumulation and alternative activation of CD11b+ cDC in the LALN, which in turn alters Th1/Th2 balance to promote fungal persistence and dissemination. |
topic |
scavenger receptor macrophage receptor with collagenous structure fungal persistence Th2 response CD11b+ conventional DC Cryptococcus neoformans |
url |
http://journal.frontiersin.org/article/10.3389/fimmu.2017.01231/full |
work_keys_str_mv |
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doaj-c3a53d522c004326a7ab4bd155f21d852020-11-24T23:53:27ZengFrontiers Media S.A.Frontiers in Immunology1664-32242017-09-01810.3389/fimmu.2017.01231286524Exploitation of Scavenger Receptor, Macrophage Receptor with Collagenous Structure, by Cryptococcus neoformans Promotes Alternative Activation of Pulmonary Lymph Node CD11b+ Conventional Dendritic Cells and Non-Protective Th2 BiasJintao Xu0Jintao Xu1Adam Flaczyk2Lori M. Neal3Lori M. Neal4Zhenzong Fa5Daphne Cheng6Mike Ivey7Bethany B. Moore8Bethany B. Moore9Jeffrey L. Curtis10Jeffrey L. Curtis11John J. Osterholzer12John J. Osterholzer13Michal A. Olszewski14Michal A. Olszewski15Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, United StatesDepartment of Veterans Affairs Health System, VA Ann Arbor Healthcare System (VHA), Ann Arbor, MI, United StatesDepartment of Veterans Affairs Health System, VA Ann Arbor Healthcare System (VHA), Ann Arbor, MI, United StatesDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, United StatesDepartment of Veterans Affairs Health System, VA Ann Arbor Healthcare System (VHA), Ann Arbor, MI, United StatesDepartment of Veterans Affairs Health System, VA Ann Arbor Healthcare System (VHA), Ann Arbor, MI, United StatesDepartment of Veterans Affairs Health System, VA Ann Arbor Healthcare System (VHA), Ann Arbor, MI, United StatesDepartment of Veterans Affairs Health System, VA Ann Arbor Healthcare System (VHA), Ann Arbor, MI, United StatesDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, United StatesDepartment of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, MI, United StatesDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, United StatesDepartment of Veterans Affairs Health System, VA Ann Arbor Healthcare System (VHA), Ann Arbor, MI, United StatesDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, United StatesDepartment of Veterans Affairs Health System, VA Ann Arbor Healthcare System (VHA), Ann Arbor, MI, United StatesDivision of Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Michigan Health System, Ann Arbor, MI, United StatesDepartment of Veterans Affairs Health System, VA Ann Arbor Healthcare System (VHA), Ann Arbor, MI, United StatesMacrophage receptor with collagenous structure (MARCO) contributes to fungal containment during the early/innate phase of cryptococcal infection; however, its role in adaptive antifungal immunity remains unknown. Using a murine model of cryptococcosis, we compared host adaptive immune responses in wild-type and MARCO−/− mice throughout an extended time course post-infection. Unlike in early infection, MARCO deficiency resulted in improved pulmonary fungal clearance and diminished cryptococcal dissemination during the efferent phase. Improved fungal control in the absence of MARCO expression was associated with enhanced hallmarks of protective Th1-immunity, including higher frequency of pulmonary TNF-α-producing T cells, increased cryptococcal-antigen-triggered IFN-γ and TNF-α production by splenocytes, and enhanced expression of M1 polarization genes by pulmonary macrophages. Concurrently, we found lower frequencies of IL-5- and IL-13-producing T cells in the lungs, impaired production of IL-4 and IL-10 by cryptococcal antigen-pulsed splenocytes, and diminished serum IgE, which were hallmarks of profoundly suppressed efferent Th2 responses in MARCO-deficient mice compared to WT mice. Mechanistically, we found that MARCO expression facilitated early accumulation and alternative activation of CD11b+ conventional DC (cDC) in the lung-associated lymph nodes (LALNs), which contributed to the progressive shift of the immune response from Th1 toward Th2 at the priming site (LALNs) and local infection site (lungs) during the efferent phase of cryptococcal infection. Taken together, our study shows that MARCO can be exploited by the fungal pathogen to promote accumulation and alternative activation of CD11b+ cDC in the LALN, which in turn alters Th1/Th2 balance to promote fungal persistence and dissemination.http://journal.frontiersin.org/article/10.3389/fimmu.2017.01231/fullscavenger receptor macrophage receptor with collagenous structurefungal persistenceTh2 responseCD11b+ conventional DCCryptococcus neoformans |