Migrating lung monocytes internalize and inhibit growth of Aspergillus fumigatus conidia

AbstractMonocytes are important players to combat ubiquitously present fungus Aspergillus fumigatus. Recruitment of monocytes to sites of fungal infection was shown in vivo, and purified murine and human blood monocytes are able to induce inflammatory and fungicidal mediators as well as the host cell and the fungal transcriptional responses upon exposure to A.fumigatus. Mononuclear tissue phagocytes are phenotypically and functionally different from those circulating in the blood and their role in antifungal defences is much less understood.In this study, we identified a population of migrating CD43+ monocytes in cells isolated from rat distal lungs. These cells phenotypically different from alveolar macrophages, showed clearly distinct locomotory behaviour on the surface of primary alveolar cells resembling previously described endothelial patrolling. The CD43+ monocytes internalized live A.fumigatus conidia resulting in inhibition of conidial germination and hyphal growth. Thus, migrating lung monocytes might play an important role in local defence against pulmonary pathogens.

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Migrating Lung Monocytes Internalize and Inhibit Growth of Aspergillus fumigatus Conidia

Pathogens ◽

10.3390/pathogens9120983 ◽

2020 ◽

Vol 9 (12) ◽

pp. 983

Author(s):

Natalia Schiefermeier-Mach ◽

Thomas Haller ◽

Stephan Geley ◽

Susanne Perkhofer

Keyword(s):

Aspergillus Fumigatus ◽

Inflammatory Cytokines ◽

Hyphal Growth ◽

Blood Monocytes ◽

Alveolar Cells ◽

Present Fungus ◽

Locomotory Behavior ◽

Patrolling Monocytes

Monocytes are important players to combat the ubiquitously present fungus Aspergillus fumigatus. Recruitment of monocytes to sites of fungal A. fumigatus infection has been shown in vivo. Upon exposure to A. fumigatus in vitro, purified murine and human blood monocytes secrete inflammatory cytokines and fungicidal mediators. Mononuclear tissue phagocytes are phenotypically and functionally different from those circulating in the blood and their role in antifungal defenses is much less understood. In this study, we identified a population of migrating CD43+ monocytes in cells isolated from rat distal lungs. These cells are phenotypically different from alveolar macrophages and show distinct locomotory behavior on the surface of primary alveolar cells resembling previously described endothelial patrolling monocytes. Upon challenge, the CD43+ monocytes internalized A. fumigatus conidia resulting in inhibition of their germination and hyphal growth. Thus, migrating lung monocytes might play an important role in local defense against pulmonary pathogens.

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Expression of LAIR-1 (CD305) on Human Blood Monocytes as a Marker of Hepatic Cirrhosis Progression

Journal of Immunology Research ◽

10.1155/2019/2974753 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 2

Author(s):

María Martínez-Esparza ◽

Antonio José Ruiz-Alcaraz ◽

Violeta Carmona-Martínez ◽

María Dolores Fernández-Fernández ◽

Gonzalo Antón ◽

...

Keyword(s):

Liver Cirrhosis ◽

Cell Surface ◽

Human Blood ◽

Total Content ◽

Cell Surface Expression ◽

Human Macrophage ◽

Blood Monocytes ◽

Cirrhotic Patients

Background and Aim. The presumed role of the inhibitory receptor LAIR-1 (CD305) in the inflammatory response suggests that it might contribute to the pathophysiology of chronic inflammatory diseases such as liver cirrhosis. We studied the LAIR-1 expression on liver macrophages and blood monocytes related to the progression of liver cirrhosis. Methods. The expression of LAIR-1 was analyzed by immunohistochemistry, flow cytometry, and Western blot. Results. We found a decreased number of macrophages expressing LAIR-1 in cirrhotic liver that could be due to a high presence of collagen, ligand of LAIR-1, in the fibrotic tissue which could downregulate its expression or interfere with the immunostaining. The expression of LAIR-1 decreased after cell differentiation, and the total content, but not the cell surface expression, increased after activation in the HL-60 human macrophage in vitro model. Blood monocytes exhibited higher LAIR-1 expression levels in cirrhotic patients, which were evident even in early clinical stages in all monocyte subsets, and greater in the “intermediate” inflammatory monocyte subpopulation. The in vitro activation of human blood monocytes did not increase its expression on the cell surface suggesting that the in vivo increase of LAIR-1 must be the result of a specific combination of stimuli present in cirrhotic patients. This represents an exclusive feature of liver cirrhosis, since blood monocytes from other chronic inflammatory pathologies showed similar or lower LAIR-1 levels compared with those of healthy controls. Conclusions. These results may indicate that monocyte LAIR-1 expression is a new biomarker to early detect liver damage caused by chronic inflammation in liver cirrhosis.

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Influence of phosphatidylglycerol on the uptake of liposomes by alveolar cells and on lung function

Journal of Applied Physiology ◽

10.1152/japplphysiol.01164.2004 ◽

2005 ◽

Vol 98 (5) ◽

pp. 1784-1791 ◽

Cited By ~ 5

Author(s):

D. L. H. Poelma ◽

B. Lachmann ◽

J. J. Haitsma ◽

L. J. Zimmermann ◽

J. F. van Iwaarden

Keyword(s):

Lung Function ◽

Alveolar Macrophages ◽

Alveolar Type ◽

Type Ii Cells ◽

Type Ii ◽

Negative Effects ◽

Alveolar Cells ◽

Alveolar Type Ii Cells ◽

High Concentrations

The effect of phosphatidylglycerol on the uptake of surfactant-like liposomes by alveolar type II cells and alveolar macrophages as well as the effect on endogenous surfactant function was studied in vivo. Healthy ventilated rats were intratracheally instilled with fluorescent labeled liposomes with different concentrations of phosphatidylglycerol. Lung function was determined by monitoring arterial oxygenation and, at the end of the experiment, by recording static pressure-volume curves. In addition, alveolar cells were isolated, and cell-associated fluorescence was determined using flow cytometry. The results show that, in the presence of cofactors (Ca2+, Mg2+), phosphatidylglycerol stimulates the uptake by alveolar macrophages but hardly affects the uptake by alveolar type II cells. High concentrations of phosphatidylglycerol reduce the number of alveolar macrophages in the alveolar space and deteriorate lung function. On the other hand, the presence of cofactors protects the lung against the negative effects of phosphatidylglycerol on endogenous surfactant and alveolar macrophages. This study indicates that the phosphatidylglycerol concentration may play a fundamental role in the surfactant function and metabolism depending on the presence of so-called cofactors like calcium and magnesium; further study is needed to clarify the mechanisms involved.

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Dyscoordinate Expression of Tumor Necrosis Factor-alpha by Human Blood Monocytes and Alveolar Macrophages

American Review of Respiratory Disease ◽

10.1164/ajrccm/139.4.1010 ◽

1989 ◽

Vol 139 (4) ◽

pp. 1010-1016 ◽

Cited By ~ 53

Author(s):

Elizabeth A. Rich ◽

James R. Panuska ◽

Robert S. Wallis ◽

Christopher B. Wolf ◽

Michelle L. Leonard ◽

...

Keyword(s):

Tumor Necrosis Factor ◽

Tumor Necrosis Factor Alpha ◽

Human Blood ◽

Alveolar Macrophages ◽

Tumor Necrosis ◽

Blood Monocytes ◽

Necrosis Factor Alpha ◽

Factor Alpha ◽

Necrosis Factor

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Tetraspanins CD9 and CD81 function to prevent the fusion of mononuclear phagocytes

The Journal of Cell Biology ◽

10.1083/jcb.200212031 ◽

2003 ◽

Vol 161 (5) ◽

pp. 945-956 ◽

Cited By ~ 123

Author(s):

Yoshito Takeda ◽

Isao Tachibana ◽

Kenji Miyado ◽

Masatoshi Kobayashi ◽

Toru Miyazaki ◽

...

Keyword(s):

Complex Formation ◽

Alveolar Macrophages ◽

Bone Marrow Cells ◽

Giant Cells ◽

Mononuclear Phagocytes ◽

Blood Monocytes ◽

Multinucleated Cells ◽

Infected Cells

Tetraspanins CD9 and CD81 facilitate the fusion between gametes, myoblasts, or virus-infected cells. Here, we investigated the role of these tetraspanins in the fusion of mononuclear phagocytes. Expression of CD9 and CD81 and their complex formation with integrins were up-regulated when blood monocytes were cultured under normal conditions. Under fusogenic conditions in the presence of Con A, CD9 and CD81 up-regulation was inhibited, and their complex formation with integrins was down-regulated. Anti-CD9 and -CD81 antibodies, which were previously shown to inhibit the fusion of gametes, myoblasts, and virus-infected cells, unexpectedly promoted the fusion of monocytes and alveolar macrophages. However, these effects were not due to altered cell adhesion, aggregation, or cytokine production. When stimulated in vitro or in vivo, alveolar macrophages and bone marrow cells of CD9- and CD81-null mice formed larger numbers of multinucleated cells than those of wild-type mice. Finally, CD9/CD81 double-null mice spontaneously developed multinucleated giant cells in the lung and showed enhanced osteoclastogenesis in the bone. These results suggest that CD9 and CD81 coordinately prevent the fusion of mononuclear phagocytes.

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Distinct effects of SP-B and SP-C on the uptake of surfactant-like liposomes by alveolar cells in vivo and in vitro

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00054.2004 ◽

2004 ◽

Vol 287 (5) ◽

pp. L1056-L1065 ◽

Cited By ~ 10

Author(s):

D. L. H. Poelma ◽

L. J. Zimmermann ◽

W. A. van Cappellen ◽

J. J. Haitsma ◽

B. Lachmann ◽

...

Keyword(s):

Alveolar Macrophages ◽

Divalent Cations ◽

Alveolar Type ◽

Type Ii Cells ◽

Type Ii ◽

Alveolar Cells ◽

Alveolar Type Ii Cells ◽

Lipid Ratio

The effects of surfactant protein B (SP-B) and SP-C on the uptake of surfactant-like liposomes by alveolar type II cells and alveolar macrophages were studied both in vivo and in vitro. In vivo, mechanically ventilated rats were intratracheally instilled with fluorescently labeled liposomes that had SP-B and/or SP-C incorporated in different concentrations. Consequently, the alveolar cells were isolated, and cell-associated fluorescence was determined using flow cytometry. The results show that the incorporation of SP-B does not influence the uptake, and it also does not in the presence of essential cofactors. The inclusion of SP-C in the liposomes enhanced the alveolar type II cells at a SP-C to lipid ratio of 2:100. If divalent cations (calcium and magnesium) were present at physiological concentrations in the liposome suspension, uptake of liposomes by alveolar macrophages was also enhanced. In vitro, the incorporation of SP-B affected uptake only at a protein-to-lipid ratio of 8:100, whereas the inclusion of SP-C in the liposomes leads to an increased uptake at a protein-to-lipid ratio of 1:100. From these results, it can be concluded that SP-B is unlikely to affect uptake of surfactant, whereas SP-C in combination with divalent cations and other solutes are capable of increasing the uptake.

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