Methylprednisolone impairs conidial phagocytosis but does not attenuate hyphal damage by neutrophils against Exserohilum rostratum

Simitsopoulou, Maria; Walsh, Thomas J.; Kyrpitzi, Daniela; Petraitis, Vidmantas; Kontoyiannis, Dimitrios P.; Perlin, David S.; Roilides, Emmanuel

doi:10.1093/mmy/myu034

Cited by 8 publications

(10 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Second, our in vitro work shows that corticosteroids significantly reduce the level of production of TNF-␣ by macrophages, which may influence the recruitment of additional immune cells to the site of infection. Third, methylprednisolone decreases the phagocytic activity of neutrophils toward Exserohilum (77). All of these factors may contribute to the lack of immune cell recruitment at the initial site of infection and the enhanced hyphal growth in tissue.…”

Section: Discussionmentioning

confidence: 99%

The Carbohydrate Lectin Receptor Dectin-1 Mediates the Immune Response to Exserohilum rostratum

et al. 2017

View full text Add to dashboard Cite

Dematiaceous molds are found ubiquitously in the environment and cause a wide spectrum of human disease, including infections associated with high rates of mortality. Despite this, the mechanism of the innate immune response has been less well studied, although it is key in the clearance of fungal pathogens. Here, we focus on Exserohilum rostratum, a dematiaceous mold that caused 753 infections during a multistate outbreak due to injection of contaminated methylprednisolone. We show that macrophages are incapable of phagocytosing Exserohilum. Despite a lack of phagocytosis, macrophage production of tumor necrosis factor alpha is triggered by hyphae but not spores and depends upon Dectin-1, a C-type lectin receptor. Dectin-1 is specifically recruited to the macrophage-hyphal interface but not the macrophage-spore interface due to differences in carbohydrate antigen expression between these two fungal forms. Corticosteroid and antifungal therapy perturb this response, resulting in decreased cytokine production. In vivo soft tissue infection in wild-type mice demonstrated that Exserohilum provokes robust neutrophilic and granulomatous inflammation capable of thwarting fungal growth. However, coadministration of methylprednisolone acetate results in robust hyphal tissue invasion and a significant reduction in immune cell recruitment. Our results suggest that Dectin-1 is crucial for macrophage recognition and the macrophage response to Exserohilum and that corticosteroids potently attenuate the immune response to this pathogen.

show abstract

Section: Discussionmentioning

confidence: 99%

The Carbohydrate Lectin Receptor Dectin-1 Mediates the Immune Response to Exserohilum rostratum

et al. 2017

View full text Add to dashboard Cite

show abstract

“…A recent report (9) suggested that methylprednisolone-induced suppression of phagocytosis by polymorphonuclear leukocytes was responsible for the rapid development of an E. rostratum outbreak in the United States. The therapeutic approach to combat this pathogen has not yet been established; therefore, knowledge regarding its pathogenic potential and antifungal susceptibility is of paramount importance (8,10,11).…”

mentioning

confidence: 99%

In Vitro Activities of Eight Antifungal Drugs against a Global Collection of Genotyped Exserohilum Isolates

Chowdhary

Hagen

Curfs-Breuker

et al. 2015

Antimicrob Agents Chemother

View full text Add to dashboard Cite

eThe in vitro susceptibilities of 24 worldwide Exserohilum isolates belonging to 10 species from human and environmental sources were determined for eight antifungal drugs. The strains were characterized by internal transcribed spacer (ITS) sequencing and amplified fragment length polymorphism fingerprinting. Posaconazole had the lowest geometric mean MIC (0.16 g/ ml), followed by micafungin (0.21 g/ml), amphotericin B (0.24 g/ml), itraconazole (0.33 g/ml), voriconazole (0.8 g/ml), caspofungin (1.05 g/ml), isavuconazole (1.38 g/ml), and fluconazole (15.6 g/ml).

show abstract

“…8 La metilprednisolona reduce la expresión de la molécula de adhesión LFA-1 (antígeno-1 asociado a la función leucocitaria) necesaria para la emigración transendotelial de leucocitos a través del endotelio. 7 Los neutrófilos separados de la sangre periférica de adultos que reciben metilprednisolona endovenosa por 5 días presentan in vitro reducción de la etapa de ingestión de Exserohilum rostratum, lo que propicia meningitis, 9 semejante a lo observado en el presente estudio. Durante la corticoterapia se registra aspergilosis pulmonar invasiva, que también depende de la perfecta función neutrofílica.…”

unclassified

“…Varios otros inmunosupreCuadro 2. Fenotipos de linfocitos e inmunoglobulinas séricas de niña de 2 años en el segundo día postrasplante intestinal, comparados con las curvas de referencia de niños saludables de la misma edad 6,9 Fenotipo de linfocitos (células/mm3) Valores sin diferencias significativas sores actúan de forma análoga, además de enmascarar las manifestaciones clínicas de la infección. Tanto la cirugía mayor como los inmunosupresores utilizados pudieron alterar la función neutrofílica en la paciente que se describe en este informe.…”

unclassified

“…Tanto la cirugía mayor como los inmunosupresores utilizados pudieron alterar la función neutrofílica en la paciente que se describe en este informe. 8,9,10 El trastorno neutrofílico propició mayor susceptibilidad de la paciente a la infección hospitalaria por Staphylococcus aureus, una vez que la defensa contra tal patógeno necesitó la perfecta actividad de fagocitos neutrofílicos. …”

unclassified

See 1 more Smart Citation

Alteración laboratorial que precede a las manifestaciones clínicas de infección estafilocócica postrasplante intestinal

Forte

Galvan

Salem-Molino

et al. 2017

RAM

View full text Add to dashboard Cite

Este artículo debe citarse como: Carvalho Neves-Forte W, Carvalho-Galvan AO, Salem-Molino P, Roque T, Mosca T, Soler W. Alteración laboratorial que precede a las manifestaciones clínicas de infección estafilocócica postrasplante intestinal. Rev Alerg Mex. 2017;64(3):381-385 AbstractBackground: Hospital-acquired infection, often with Staphylococcus aureus, is an important complication in intestinal transplant. Clinical case: A 2-year-old girl underwent small bowel transplantation owing to a small bowel volvulus. On the first postoperative day, lymphocyte phenotypes, serum immunoglobulins and chemotactic and phagocytic activity of neutrophils were assessed in peripheral blood. A decrease in the ingestion phase of phagocytosis by neutrophils was identified, in comparison with the results of 20 healthy children. On the second day, the patient had low fever and, on the third, abdominal pain. In view of this, she underwent a laparotomy that revealed purulent ascites due to Staphylococcus aureus. Specific treatment resulted in rapid regression of the infectious condition and good evolution of the patient. Conclusions: A decrease in the ingestion stage of phagocytosis by neutrophils preceded staphylococcal purulent ascites clinical manifestations, and immunologic assessment contributed to early diagnosis and treatment of the infection. We believe evaluation of neutrophilic activity is important in patients undergoing intestinal transplantation in order for possible hospital-acquired infections to be early diagnosed.

show abstract

Methylprednisolone impairs conidial phagocytosis but does not attenuate hyphal damage by neutrophils against Exserohilum rostratum

Cited by 8 publications

References 16 publications

The Carbohydrate Lectin Receptor Dectin-1 Mediates the Immune Response to Exserohilum rostratum

The Carbohydrate Lectin Receptor Dectin-1 Mediates the Immune Response to Exserohilum rostratum

In Vitro Activities of Eight Antifungal Drugs against a Global Collection of Genotyped Exserohilum Isolates

Alteración laboratorial que precede a las manifestaciones clínicas de infección estafilocócica postrasplante intestinal

Contact Info

Product

Resources

About