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Shankar, Madhu
Publications (2 of 2) Show all publications
Shankar, M., Uwamahoro, N., Backman, E., Holmberg, S., Niemiec, M. J., Roth, J., . . . Urban, C. F. (2021). Immune Resolution Dilemma: Host Antimicrobial Factor S100A8/A9 Modulates Inflammatory Collateral Tissue Damage During Disseminated Fungal Peritonitis. Frontiers in Immunology, 12, Article ID 553911.
Open this publication in new window or tab >>Immune Resolution Dilemma: Host Antimicrobial Factor S100A8/A9 Modulates Inflammatory Collateral Tissue Damage During Disseminated Fungal Peritonitis
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2021 (English)In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 12, article id 553911Article in journal (Refereed) Published
Abstract [en]

Intra-abdominal infection (peritonitis) is a leading cause of severe disease in surgical intensive care units, as over 70% of patients diagnosed with peritonitis develop septic shock. A critical role of the immune system is to return to homeostasis after combating infection. S100A8/A9 (calprotectin) is an antimicrobial and pro-inflammatory protein complex used as a biomarker for diagnosis of numerous inflammatory disorders. Here we describe the role of S100A8/A9 in inflammatory collateral tissue damage (ICTD). Using a mouse model of disseminated intra-abdominal candidiasis (IAC) in wild-type and S100A8/A9-deficient mice in the presence or absence of S100A9 inhibitor paquinimod, the role of S100A8/A9 during ICTD and fungal clearance were investigated. S100A8/A9-deficient mice developed less ICTD than wild-type mice. Restoration of S100A8/A9 in knockout mice by injection of recombinant protein resulted in increased ICTD and fungal clearance comparable to wild-type levels. Treatment with paquinimod abolished ICTD and S100A9-deficient mice showed increased survival compared to wild-type littermates. The data indicates that S100A8/A9 controls ICTD levels and antimicrobial activity during IAC and that targeting of S100A8/A9 could serve as promising adjunct therapy against this challenging disease.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2021
Keywords
Candida albicans, host-pathogen interactions, host-targeted agents, inflammation, peritonitis, S100A8/A9 complex, sepsis
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-181798 (URN)10.3389/fimmu.2021.553911 (DOI)000627778800001 ()2-s2.0-85102439343 (Scopus ID)
Funder
The Kempe Foundations, SMK-1453Swedish Research Council, VR-M 2017-01681Swedish Research Council, 2014-02281
Available from: 2021-04-01 Created: 2021-04-01 Last updated: 2024-08-05Bibliographically approved
Niemiec, M. J., Grumaz, C., Ermert, D., Desel, C., Shankar, M., Lopes, J. P., . . . Urban, C. F. (2017). Dual transcriptome of the immediate neutrophil and Candida albicans interplay. BMC Genomics, 18, Article ID 696.
Open this publication in new window or tab >>Dual transcriptome of the immediate neutrophil and Candida albicans interplay
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2017 (English)In: BMC Genomics, E-ISSN 1471-2164, Vol. 18, article id 696Article in journal (Refereed) Published
Abstract [en]

Background: Neutrophils are traditionally considered transcriptionally inactive. Compared to other immune cells, little is known about their transcriptional profile during interaction with pathogens. Methods: We analyzed the meta-transcriptome of the neutrophil-Candida albicans interplay and the transcriptome of C. albicans challenged with neutrophil extracellular traps (NETs) by RNA-Seq, considering yeast and hypha individually in each approach. Results: The neutrophil response to C. albicans yeast and hyphae was dominated by a morphotype-independent core response. However, 11 % of all differentially expressed genes were regulated in a specific manner when neutrophils encountered the hyphal form of C. albicans. While involving genes for transcriptional regulators, receptors, and cytokines, the neutrophil core response lacked typical antimicrobial effectors genes. Genes of the NOD-like receptor pathway, including NLRP3, were enriched. Neutrophil-and NET-provoked responses in C. albicans differed. At the same time, the Candida transcriptome upon neutrophil encounter and upon NET challenge included genes from various metabolic processes and indicate a mutual role of the regulators Tup1p, Efg1p, Hap43p, and Cap1p. Upon challenge with neutrophils and NETs, the overall Candida response was partially morphotype-specific. Yet again, actual oppositional regulation in yeasts and hyphae was only detected for the arginine metabolism in neutrophil-infecting C. albicans. Conclusions: Taken together, our study provides a comprehensive and quantitative transcript profile of the neutrophil-C. albicans interaction. By considering the two major appearances of both, neutrophils and C. albicans, our study reveals yet undescribed insights into this medically relevant encounter. Hence, our findings will facilitate future research and potentially inspire novel therapy developments.

Keywords
Candida, Neutrophils, Dual transcriptome, Extracellular traps, NOD-like receptor pathway, Nutritional immunity, Morphotype
National Category
Microbiology in the medical area
Research subject
Clinical Bacteriology
Identifiers
urn:nbn:se:umu:diva-102836 (URN)10.1186/s12864-017-4097-4 (DOI)000409208200002 ()2-s2.0-85028808388 (Scopus ID)
Note

Originally published in manuscript form with title [RNA-Seq transcription profile of the neutrophil: Candida albicans in vitro interaction]

Errata BMC Genomics (2017) 18:696 DOI: 10.1186/s12864-017-4097-4

Available from: 2015-05-07 Created: 2015-05-07 Last updated: 2024-07-02Bibliographically approved
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