Global Transcriptomic Profiling of Innate and Adaptive Immunity During Aspergillus flavus Endophthalmitis in a Murine Model

被引:1
作者
Khapuinamai, Agimanailiu [1 ,2 ]
Rudraprasad, Dhanwini [1 ,2 ]
Pandey, Suchita [1 ]
Gandhi, Jaishree [1 ]
Mishra, Dilip Kumar [3 ]
Joseph, Joveeta [1 ,4 ]
机构
[1] L V Prasad Eye Inst, Jhaveri Microbiol Ctr, Brien Holden Eye Res Ctr, Hyderabad, Telangana, India
[2] Manipal Acad Higher Educ, Ctr Doctoral Studies, Manipal, Karnataka, India
[3] L V Prasad Eye Inst, Ocular Pathol Serv, Hyderabad, India
[4] L V Prasad Eye Inst, Head Microbiol LVPEI Network, Jhaveri Microbiol Ctr, Kallam Anji Reddy Campus, Hyderabad 500034, India
关键词
endophthalmitis; Aspergillus flavus ( A. flavus ); transcriptomics; RNA-seq; adaptive immunity; PROTEIN-TYROSINE KINASE; T-CELL-ACTIVATION; DIACYLGLYCEROL KINASES; CLINICAL PRESENTATIONS; HOST-DEFENSE; RECEPTORS; INFLAMMATION; COMBINATION; CULTURE; POLYENE;
D O I
10.1167/iovs.65.4.44
中图分类号
R77 [眼科学];
学科分类号
100212 ;
摘要
PURPOSE . Fungal endophthalmitis is characterized by chronic inflammation leading to the partial or complete vision loss. Herein, we analyzed the transcriptomic landscape of Aspergillus flavu s ( A. flavus ) endophthalmitis in C57BL/6 mice to understand the host-pathogen interactions. METHODS . Endophthalmitis was induced by intravitreal injection of A. flavus spores in C57BL/6 mice and monitored for disease progression up to 72 hours. The enucleated eyeballs were subjected to histopathological analysis and mRNA sequencing using the Illumina Nextseq 2000. Pathway enrichment analysis was performed to further annotate the functions of differentially expressed genes (DEGs) and validation of cytokines was performed in vitreous of patients with fungal endophthalmitis using multiplex ELISA. RESULTS . Transcriptomic landscape of A. flavus endophthalmitis revealed upregulated T-cell receptor signaling, PI3K-AKT, MAPK, NF- kappa B, JAK -STAT, and NOD like receptor signaling pathways. We observed significant increase in the T-cells during infection especially at 72 hours infection along with elevated expression levels of IL -6, IL -10, IL -12, IL -18, IL -19, IL -23, CCR3, and CCR7. Furthermore, host -immune response associated genes, such as T-cell interacting activating receptor, TNF receptor-associated factor 1, TLR1, TLR9, and bradykinin receptor beta 1, were enriched. Histopathological assessment validated the significant increase in inflammatory cells, especially T-cells at 72 hours post-infection along with increased disruption in the retinal architecture. Additionally, IL -6, IL -8, IL -17, TNF- alpha , and IL-1 beta were also significantly elevated, whereas IL -10 was downregulated in vitreous of patients with Aspergillus endophthalmitis. CONCLUSIONS . Regulating T-cell influx could be a potential strategy to modulate the excessive inflammation in the retina and potentially aid in better vision recovery in fungal endophthalmitis.
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页数:16
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共 68 条
  • [1] Immunomodulation for the Treatment of Fungal Infections: Opportunities and Challenges
    Ademe, Muluneh
    [J]. FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, 2020, 10
  • [2] TNF plays a crucial role in inflammation by signaling via T cell TNFR2
    Alam, Muhammad S.
    Otsuka, Shizuka
    Wong, Nathan
    Abbasi, Aamna
    Gaida, Matthias M.
    Fan, Yu
    Meerzaman, Daoud
    Ashwell, Jonathan D.
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2021, 118 (50)
  • [3] The role of NOD-like receptors in innate immunity
    Almeida-da-Silva, Cassio Luiz Coutinho
    Savio, Luiz Eduardo Baggio
    Coutinho-Silva, Robson
    Ojcius, David M.
    [J]. FRONTIERS IN IMMUNOLOGY, 2023, 14
  • [4] The human C-type lectin CLECSF8 is a novel monocyte/macrophage endocytic receptor
    Arce, I
    Martínez-Muñoz, L
    Roda-Navarro, P
    Fernández-Ruiz, E
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 2004, 34 (01) : 210 - 220
  • [5] Treatment of two postoperative endophthalmitis cases due to Aspergillus flavus and Scopulariopsis spp.: with local and systemic antifungal therapy
    Aydin, Sayime
    Ertugrul, Bulent
    Gultekin, Berna
    Uyar, Guliz
    Kir, Erkin
    [J]. BMC INFECTIOUS DISEASES, 2007, 7
  • [6] Overview of the immune response
    Chaplin, David D.
    [J]. JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2010, 125 (02) : S3 - S23
  • [7] CHEN WF, 1991, J IMMUNOL, V147, P528
  • [8] Retinal cell death and current strategies in retinal neuroprotection
    Chinskey, Nicholas D.
    Besirli, Cagri G.
    Zacks, David N.
    [J]. CURRENT OPINION IN OPHTHALMOLOGY, 2014, 25 (03) : 228 - 233
  • [9] The Role of Formyl Peptide Receptors in Permanent and Low-Grade Inflammation: Helicobacter pylori Infection as a Model
    Cuomo, Paola
    Papaianni, Marina
    Capparelli, Rosanna
    Medaglia, Chiara
    [J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2021, 22 (07)
  • [10] The Diagnosis and Treatment of Fungal Endophthalmitis: An Update
    Danielescu, Ciprian
    Stanca, Horia Tudor
    Iorga, Raluca-Eugenia
    Darabus, Diana-Maria
    Potop, Vasile
    [J]. DIAGNOSTICS, 2022, 12 (03)