Neutrophils Mediate Maturation and Efflux of Lung Dendritic Cells in Response to Aspergillus fumigatus Germ Tubes

Park, Stacy J.; Burdick, Marie D.; Mehrad, Borna

doi:10.1128/iai.00097-12

Cited by 47 publications

(39 citation statements)

References 36 publications

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“…iNOS, inducible nitric oxide synthase. DC observed in wild-type infected lungs and absent from CCR2-deficient mice are similar to those in invasive pulmonary aspergillosis (42,43) and differ from the TNF-and iNOS-producing DC (Tip-DC) first described in the spleens of animals with listeriosis (52) in that they do not express iNOS. At the early time points that we examined, we did not find any lung macrophages expressing M2 markers in either wild-type or CCR2-deficient mice, indicating that CCR2 is either necessary for recruitment of M1 macrophage precursors or for their development in the lung from uncommitted precursors.…”

Section: L706mentioning

confidence: 68%

Heterogeneity of lung mononuclear phagocytes during pneumonia: contribution of chemokine receptors

Chen

Zhang

Barletta³

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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Bacterial pneumonia is a common and dangerous illness. Mononuclear phagocytes, which comprise monocyte, resident and recruited macrophage, and dendritic cell subsets, are critical to antimicrobial defenses, but the dynamics of their recruitment to the lungs in pneumonia is not established. We hypothesized that chemokine-mediated traffic of mononuclear phagocytes is important in defense against bacterial pneumonia. In a mouse model of Klebsiella pneumonia, circulating Ly6Chi and, to a lesser extent, Ly6Clo monocytes expanded in parallel with accumulation of inflammatory macrophages and CD11bhi dendritic cells and plasmacytoid dendritic cells in the lungs, whereas numbers of alveolar macrophages remained constant. CCR2 was expressed by Ly6Chi monocytes, recruited macrophages, and airway dendritic cells; CCR6 was prominently expressed by airway dendritic cells; and CX3CR1 was ubiquitously expressed by blood monocytes and lung CD11bhi dendritic cells during infection. CCR2-deficient, but not CCL2-, CX3CR1-, or CCR6-deficient animals exhibited worse outcomes of infection. The absence of CCR2 had no detectable effect on neutrophils but resulted in reduction of all subsets of lung mononuclear phagocytes in the lungs, including alveolar macrophages and airway and plasmacytoid dendritic cells. In addition, absence of CCR2 skewed the phenotype of lung mononuclear phagocytes, abrogating the appearance of M1 macrophages and TNF-producing dendritic cells in the lungs. Taken together, these data define the dynamics of mononuclear phagocytes during pneumonia.

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Section: L706mentioning

confidence: 68%

Heterogeneity of lung mononuclear phagocytes during pneumonia: contribution of chemokine receptors

Chen

Zhang

Barletta³

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Additionally, the absence of both cell types might result in the recruitment of other effector cells that ultimately enhance protection. For example, in neutropenic mice infected with A. fumigatus, DC recruitment and maturation were enhanced (44), and it is possible that an additional eosinophil deficiency would stimulate further enhancement. Therefore, an important direction for further study is evaluation of the role of eosinophils and other host effector cells and molecules that ultimately drive protective or pathogenic immune responses to fungal infection.…”

Section: Discussionmentioning

confidence: 99%

Eosinophils Are Recruited in Response to Chitin Exposure and Enhance Th2-Mediated Immune Pathology in Aspergillus fumigatus Infection

O'Dea

Amarsaikhan

et al. 2014

Infect Immun

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In patients infected with the fungus Aspergillus fumigatus, Th1 responses are considered protective, while Th2 responses are associated with increased morbidity and mortality. How host-pathogen interactions influence the development of these protective or detrimental immune responses is not clear. We compared lung immune responses to conidia from two fungal isolates that expressed different levels of the fungal cell wall component chitin. We observed that repeated aspirations of the high-chitinexpressing isolate Af5517 induced increased airway eosinophilia in the lungs of recipient mice compared to the level of eosinophilia induced by isolate Af293. CD4؉ T cells in the bronchoalveolar lavage fluid (BALF) of Af5517-aspirated mice displayed decreased gamma interferon secretion and increased interleukin-4 transcription. In addition, repeated aspirations of Af5517 induced lung transcription of the Th2-associated chemokines CCL11 (eotaxin-1) and CCL22 (macrophage-derived chemokine). Eosinophil recruitment in response to conidial aspiration was correlated with the level of chitin exposure during germination and was decreased by constitutive lung chitinase expression. Moreover, eosinophil-deficient mice subjected to multiple aspirations of Af5517 prior to neutrophil depletion and infection exhibited decreased morbidity and fungal burden compared to the levels of morbidity and fungal burden found in wild-type mice. These results suggest that exposure of chitin in germinating conidia promotes eosinophil recruitment and ultimately induces Th2-skewed immune responses after repeated aspiration. Furthermore, our results suggest that eosinophils should be examined as a potential therapeutic target in patients that mount poorly protective Th2 responses to A. fumigatus infection.

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“…A recent follow-up to this study determined that DCs recruited in the absence of neutrophils display a more immature phenotype [16] . In fact, when neutrophils are cocultured with DCs, an increase in costimulatory molecule expression occurs, a process that requires the C-type lectin receptor, DC-SIGN.…”

Section: Introductionmentioning

confidence: 99%

Innate Lung Defense during Invasive Aspergillosis: New Mechanisms

Garth¹,

Steele²

2017

J Innate Immun

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Invasive aspergillosis (IA) is one of the most difficult to treat and, consequently, one of the most lethal fungal infections known to man. Continued use of immunosuppressive agents during chemotherapy and organ transplantation often leads to the development of neutropenia, the primary risk factor for IA. However, IA is also becoming more appreciated in chronic diseases associated with corticosteroid therapy. The innate immune response to Aspergillus fumigatus, the primary agent in IA, plays a pivotal role in the recognition and elimination of organisms from the pulmonary system. This review highlights recent findings about innate host defense mechanisms, including novel aspects of innate cellular immunity and pathogen recognition, and the inflammatory mediators that control infection with A. fumigatus.

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Neutrophils Mediate Maturation and Efflux of Lung Dendritic Cells in Response to Aspergillus fumigatus Germ Tubes

Cited by 47 publications

References 36 publications

Heterogeneity of lung mononuclear phagocytes during pneumonia: contribution of chemokine receptors

Heterogeneity of lung mononuclear phagocytes during pneumonia: contribution of chemokine receptors

Eosinophils Are Recruited in Response to Chitin Exposure and Enhance Th2-Mediated Immune Pathology in Aspergillus fumigatus Infection

Innate Lung Defense during Invasive Aspergillosis: New Mechanisms

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