title: Differential modulation of immune response and cytokine profiles in the bursae and spleen of chickens infected with very virulent infectious bursal disease virus.
abstract: BACKGROUND
  Very virulent infectious bursal disease virus (vvIBDV) induces immunosuppression and inflammation in young birds, which subsequently leads to high mortality. In addition, infectious bursal disease (IBD) is one of the leading causes of vaccine failure on farms. Therefore, understanding the immunopathogenesis of IBDV in both the spleen and the bursae could help effective vaccine development. However, previous studies only profiled the differential expression of a limited number of cytokines, in either the spleen or the bursae of Fabricius of IBDV-infected chickens. Thus, this study aims to evaluate the in vitro and in vivo immunoregulatory effects of vvIBDV infection on macrophage-like cells, spleen and bursae of Fabricius.
  
  
  RESULTS
  The viral load was increased during the progression of the in vitro infection in the HD11 macrophage cell line and in vivo, but no significant difference was observed between the spleen and the bursae tissue. vvIBDV infection induced the expression of pro-inflammatory and Th1 cytokines, and chemokines from HD11 cells in a time- and dosage-dependent manner. Furthermore, alterations in the lymphocyte populations, cytokine and chemokine expression, were observed in the vvIBDV-infected spleens and bursae. A drastic rise was detected in numbers of macrophages and pro-inflammatory cytokine expression in the spleen, as early as 2 days post-infection (dpi). On 4 dpi, macrophage and T lymphocyte infiltration, associated with the peak expression of pro-inflammatory cytokines in the bursae tissues of infected chickens were observed. The majority of the significantly regulated pro-inflammatory cytokines and chemokines, in vvIBDV-infected spleens and bursae, were also detected in vvIBDV-infected HD11 cells. This cellular infiltration subsequently resulted in a sharp rise in nitric oxide (NO) and lipid peroxidation levels.
  
  
  CONCLUSIONS
  This study suggests that macrophage may play an important role in regulating the early expression of pro-inflammatory cytokines, first in the spleen and then in the bursae, the latter tissue undergoing macrophage infiltration at 4 dpi.
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia. m_rasoli_p@yahoo.com.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Rasoli
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia. skyeap2005@gmail.com.
authors.forename: Swee Keong
authors.initials: SK
authors.lastname: Yeap
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia. tansheauwei@gmail.com.
authors.forename: Sheau Wei
authors.initials: SW
authors.lastname: Tan
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia. kiarash.roohani@gmail.com.
authors.forename: Kiarash
authors.initials: K
authors.lastname: Roohani
authors.affiliation: Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia. kristeenyewen@hotmail.com.
authors.forename: Ye Wen
authors.initials: YW
authors.lastname: Kristeen-Teo
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia. noorjahan@upm.edu.my.|Faculty of Biotechnology and Biomolecular Sciences, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia. noorjahan@upm.edu.my.
authors.forename: Noorjahan Banu
authors.initials: NB
authors.lastname: Alitheen
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia. noryasmin@upm.edu.my.|Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia. noryasmin@upm.edu.my.
authors.forename: Yasmin Abd
authors.initials: YA
authors.lastname: Rahaman
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia. aiini@upm.edu.my.|Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia. aiini@upm.edu.my.
authors.forename: Ideris
authors.initials: I
authors.lastname: Aini
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia. mdhair@upm.edu.my.|Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia. mdhair@upm.edu.my.
authors.forename: Mohd Hair
authors.initials: MH
authors.lastname: Bejo
authors.affiliation: The Roslin Institute and R(D)SVS, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, UK. pete.kaiser@roslin.ed.ac.uk.
authors.forename: Pete
authors.initials: P
authors.lastname: Kaiser
authors.affiliation: Institute of Bioscience, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia. aro@upm.edu.my.|Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, 43400, Selangor, Malaysia. aro@upm.edu.my.
authors.forename: Abdul Rahman
authors.initials: AR
authors.lastname: Omar
mesh_terms: D000818:Animals; D018175:Birnaviridae Infections / Q000276:immunology / Q000378:metabolism / Q000662:veterinary* / Q000821:virology; D002060:Bursa of Fabricius / Q000378:metabolism*; D002460:Cell Line; D002645:Chickens; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D007243:Infectious bursal disease virus / Q000472:pathogenicity*; D011201:Poultry Diseases / Q000276:immunology / Q000378:metabolism / Q000821:virology*; D012367:RNA, Viral / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms; D013154:Spleen / Q000378:metabolism; D019562:Viral Load; D014774:Virulence
chemical_list: D016207:Cytokines; D012367:RNA, Viral