Dynamics of Polarized Macrophages and Activated CD8 Cells in Heart Tissue of Atlantic Salmon Infected With Piscine Orthoreovirus-1

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2021 Oct 4

PMID 34603301

Citations 4

Authors

Muhammad Salman Malik

Ingvild Berg Nyman

Oystein Wessel

Maria K Dahle

Espen Rimstad

Affiliations

Soon will be listed here.

Abstract

Piscine orthoreovirus (PRV-1) infection causes heart and skeletal muscle inflammation (HSMI) in farmed Atlantic salmon . The virus is also associated with focal melanized changes in white skeletal muscle where PRV-1 infection of macrophages appears to be important. In this study, we studied the macrophage polarization into M1 (pro-inflammatory) and M2 (anti-inflammatory) phenotypes during experimentally induced HSMI. The immune response in heart with HSMI lesions was characterized by CD8 and MHC-I expressing cells and not by polarized macrophages. Fluorescent hybridization (FISH) assays revealed localization of PRV-1 in a few M1 macrophages in both heart and skeletal muscle. M2 type macrophages were widely scattered in the heart and were more abundant in heart compared to the skeletal muscle. However, the M2 macrophages did not co-stain for PRV-1. There was a strong cellular immune response to the infection in the heart compared to that of the skeletal muscle, seen as increased MHC-I expression, partly in cells also containing PRV-1 RNA, and a high number of cytotoxic CD8 granzyme producing cells that targeted PRV-1. In skeletal muscle, MHC-I expressing cells and CD8 cells were dispersed between myocytes, but these cells did not stain for PRV-1. Gene expression analysis by RT-qPCR complied with the FISH results and confirmed a drop in level of PRV-1 following the cell mediated immune response. Overall, the results indicated that M1 macrophages do not contribute to the initial development of HSMI. However, large numbers of M2 macrophages reside in the heart and may contribute to the subsequent fast recovery following clearance of PRV-1 infection.

Citing Articles

KLF17 is an important regulatory component of the transcriptomic response of Atlantic salmon macrophages to infection.

Perez-Stuardo D, Frazao M, Ibaceta V, Brianson B, Sanchez E, Rivas-Pardo J Front Immunol. 2024; 14:1264599.

PMID: 38162669 PMC: 10755876. DOI: 10.3389/fimmu.2023.1264599.

Cellular heterogeneity in red and melanized focal muscle changes in farmed Atlantic salmon (Salmo salar) visualized by spatial transcriptomics.

Bjorgen H, Malik S, Rimstad E, Vaadal M, Nyman I, Koppang E Cell Tissue Res. 2023; 395(2):199-210.

PMID: 38087072 PMC: 10837230. DOI: 10.1007/s00441-023-03850-x.

In-depth health surveillance and clinical nutrition in farmed Atlantic salmon: a strategic attempt to detect and mitigate an HSMI outbreak.

Rennemo J, Myrvold S, Berge K, Kileng O, Pedersen B, Aksberg D Vet Res. 2023; 54(1):3.

PMID: 36694262 PMC: 9872415. DOI: 10.1186/s13567-023-01137-1.

Sleeping With the Enemy? The Current Knowledge of Piscine Orthoreovirus (PRV) Immune Response Elicited to Counteract Infection.

Vallejos-Vidal E, Reyes-Lopez F, Sandino A, Imarai M Front Immunol. 2022; 13:768621.

PMID: 35464421 PMC: 9019227. DOI: 10.3389/fimmu.2022.768621.

References

Grayfer L, Kerimoglu B, Yaparla A, Hodgkinson J, Xie J, Belosevic M . Mechanisms of Fish Macrophage Antimicrobial Immunity. Front Immunol. 2018; 9:1105. PMC: 5985312. DOI: 10.3389/fimmu.2018.01105. View

Nakanishi T, Shibasaki Y, Matsuura Y . T Cells in Fish. Biology (Basel). 2015; 4(4):640-63. PMC: 4690012. DOI: 10.3390/biology4040640. View

Marjara I, Chikwati E, Valen E, Krogdahl A, Bakke A . Transcriptional regulation of IL-17A and other inflammatory markers during the development of soybean meal-induced enteropathy in the distal intestine of Atlantic salmon (Salmo salar L.). Cytokine. 2012; 60(1):186-96. DOI: 10.1016/j.cyto.2012.05.027. View

Wessel O, Braaen S, Alarcon M, Haatveit H, Roos N, Markussen T . Infection with purified Piscine orthoreovirus demonstrates a causal relationship with heart and skeletal muscle inflammation in Atlantic salmon. PLoS One. 2017; 12(8):e0183781. PMC: 5571969. DOI: 10.1371/journal.pone.0183781. View

Bjorgen H, Wessel O, Fjelldal P, Hansen T, Sveier H, Saebo H . Piscine orthoreovirus (PRV) in red and melanised foci in white muscle of Atlantic salmon (Salmo salar). Vet Res. 2015; 46:89. PMC: 4562189. DOI: 10.1186/s13567-015-0244-6. View

Chaves-Pozo E, Valero Y, Lozano M, Rodriguez-Cerezo P, Miao L, Campo V . Fish Granzyme A Shows a Greater Role Than Granzyme B in Fish Innate Cell-Mediated Cytotoxicity. Front Immunol. 2019; 10:2579. PMC: 6834543. DOI: 10.3389/fimmu.2019.02579. View

Malik M, Bjorgen H, Dhamotharan K, Wessel O, Koppang E, Di Cicco E . Erythroid Progenitor Cells in Atlantic Salmon () May Be Persistently and Productively Infected with Piscine Orthoreovirus (PRV). Viruses. 2019; 11(9). PMC: 6784031. DOI: 10.3390/v11090824. View

Finstad O, Dahle M, Lindholm T, Nyman I, Lovoll M, Wallace C . Piscine orthoreovirus (PRV) infects Atlantic salmon erythrocytes. Vet Res. 2014; 45:35. PMC: 4234517. DOI: 10.1186/1297-9716-45-35. View

Lovoll M, Austbo L, Jorgensen J, Rimstad E, Frost P . Transcription of reference genes used for quantitative RT-PCR in Atlantic salmon is affected by viral infection. Vet Res. 2011; 42:8. PMC: 3031228. DOI: 10.1186/1297-9716-42-8. View

10.

Godoy M, Kibenge M, Wang Y, Suarez R, Leiva C, Vallejos F . First description of clinical presentation of piscine orthoreovirus (PRV) infections in salmonid aquaculture in Chile and identification of a second genotype (Genotype II) of PRV. Virol J. 2016; 13:98. PMC: 4906990. DOI: 10.1186/s12985-016-0554-y. View

11.

Ferguson H, Kongtorp R, Taksdal T, Graham D, Falk K . An outbreak of disease resembling heart and skeletal muscle inflammation in Scottish farmed salmon, Salmo salar L., with observations on myocardial regeneration. J Fish Dis. 2005; 28(2):119-23. DOI: 10.1111/j.1365-2761.2004.00602.x. View

12.

Lassalle M, Igarashi S, Sasaki M, Wakamatsu K, Ito S, Horikoshi T . Effects of melanogenesis-inducing nitric oxide and histamine on the production of eumelanin and pheomelanin in cultured human melanocytes. Pigment Cell Res. 2003; 16(1):81-4. DOI: 10.1034/j.1600-0749.2003.00004.x. View

13.

Wiegertjes G, Wentzel A, Spaink H, Elks P, Fink I . Polarization of immune responses in fish: The 'macrophages first' point of view. Mol Immunol. 2015; 69:146-56. DOI: 10.1016/j.molimm.2015.09.026. View

14.

Gonzalez-Fernandez C, Chaves-Pozo E, Cuesta A . Identification and Regulation of Interleukin-17 (IL-17) Family Ligands in the Teleost Fish European Sea Bass. Int J Mol Sci. 2020; 21(7). PMC: 7178287. DOI: 10.3390/ijms21072439. View

15.

Mutoloki S, Cooper G, Marjara I, Koop B, Evensen O . High gene expression of inflammatory markers and IL-17A correlates with severity of injection site reactions of Atlantic salmon vaccinated with oil-adjuvanted vaccines. BMC Genomics. 2010; 11:336. PMC: 2996971. DOI: 10.1186/1471-2164-11-336. View

16.

Johansen L, Thim H, Jorgensen S, Afanasyev S, Strandskog G, Taksdal T . Comparison of transcriptomic responses to pancreas disease (PD) and heart and skeletal muscle inflammation (HSMI) in heart of Atlantic salmon (Salmo salar L). Fish Shellfish Immunol. 2015; 46(2):612-23. DOI: 10.1016/j.fsi.2015.07.023. View

17.

Munangandu H, Fredriksen B, Mutoloki S, Dalmo R, Evensen O . The kinetics of CD4+ and CD8+ T-cell gene expression correlate with protection in Atlantic salmon (Salmo salar L) vaccinated against infectious pancreatic necrosis. Vaccine. 2013; 31(15):1956-63. DOI: 10.1016/j.vaccine.2013.02.008. View

18.

Viola A, Munari F, Sanchez-Rodriguez R, Scolaro T, Castegna A . The Metabolic Signature of Macrophage Responses. Front Immunol. 2019; 10:1462. PMC: 6618143. DOI: 10.3389/fimmu.2019.01462. View

19.

Dhamotharan K, Bjorgen H, Malik M, Nyman I, Markussen T, Dahle M . Dissemination of (PRV-1) in Atlantic Salmon () during the Early and Regenerating Phases of Infection. Pathogens. 2020; 9(2). PMC: 7169402. DOI: 10.3390/pathogens9020143. View

20.

Bjorgen H, Haldorsen R, Oaland O, Kvellestad A, Kannimuthu D, Rimstad E . Melanized focal changes in skeletal muscle in farmed Atlantic salmon after natural infection with Piscine orthoreovirus (PRV). J Fish Dis. 2019; 42(6):935-945. PMC: 6850454. DOI: 10.1111/jfd.12995. View