Porcine circovirus type 2 increases interleukin-1beta and interleukin-10 production via the MyD88–NF-kappa B signaling pathway in porcine alveolar macrophages in vitro

다국어 초록 (Multilingual Abstract)

Porcine alveolar macrophages (PAMs) represent the first line of defense in the porcine lung after infection with porcine circovirus type 2 (PCV2) via the respiratory tract. However, PCV2 infection impairs the microbicidal capability of PAMs and alters cytokine production and/or secretion. At present, the reason for the imbalance of cytokines has not been fully elucidated, and the regulatory mechanisms involved are unclear. In this study, we investigated the expression levels and regulation of interleukin-1beta (IL-1b) and IL-10 in PAMs following incubation with PCV2 in vitro. Levels of IL-1b and IL-10 increased in PAM supernatants, and the distribution of nuclear factor kappa B (NF-kB) p65 staining in nucleus, expression of MyD88 and p-IkB in cytoplasm, and DNA-binding activity of NF-kB increased after incubation with PCV2, while p65 expression in PAM cytoplasm decreased. However, when PAMs were co-incubated with PCV2 and small interfering RNA targeting MyD88, those effects were reversed. Additionally, mRNA expression levels of Toll-like receptors (TLR)-2, -3, -4, -7, -8, and -9 increased when PAMs were incubated with PCV2. These results show that PCV2 induces increased IL-1b and IL-10 production in PAMs, and these changes in expression are related to the TLR–MyD88–NF-kB signaling pathway.

참고문헌 (Reference)

1 Liu J, "Two-dimensional liquid chromatography-tandem mass spectrometry coupled with isobaric tags for relative and absolute quantification (iTRAQ) labeling approach revealed first proteome profiles of pulmonary alveolar macrophages infected with porcine circovirus type 2" 79 : 72-86, 2013

2 Hertzog PJ, "The interferon in TLR signaling: more than just antiviral" 24 : 534-539, 2003

3 Yamamoto M, "Role of adaptor TRIF in the MyD88-independent Toll-like receptor signaling pathway" 301 : 640-643, 2003

4 Chae JS, "Proinflammatory cytokine expression in the lung of pigs with porcine circovirus type 2-associated respiratory disease" 90 : 321-323, 2011

5 Allan GM, "Porcine circoviruses: a review" 12 : 3-14, 2000

6 Kekarainen T, "Porcine circovirus type 2-induced interleukin-10 modulates recall antigen responses" 89 : 760-765, 2008

7 Wei L, "Porcine circovirus type 2 induces the activation of nuclear factors kappa B by IκBα degradation" 378 : 177-184, 2008

8 Yu S, "Porcine circovirus type 2 (PCV2) distribution and replication in tissues and immune cells in early infected pigs" 115 : 261-272, 2007

9 Darwich L, "Pathogenesis of postweaning multisystemic wasting syndrome caused by Porcine circovirus 2: an immune riddle" 149 : 857-874, 2004

10 Lv Y, "PCV2 induces apoptosis and modulates calcium homeostasis in piglet lymphocytes in vitro" 93 : 1525-1530, 2012

11 Krakowka S, "Mycoplasma hyopneumoniae bacterins and porcine circovirus type 2 (PCV2) infection: induction of postweaning multisystemic wasting syndrome (PMWS) in the gnotobiotic swine model of PCV2-associated disease" 48 : 716-724, 2007

12 Mosser DM, "Interleukin-10: new perspectives on an old cytokine" 226 : 205-218, 2008

13 Gilpin DF, "In vitro studies on the infection and replication of porcine circovirus type 2 in cells of the porcine immune system" 94 : 149-161, 2003

14 Chang HW, "Immunopathological effects of porcine circovirus type 2 (PCV2) on swine alvelolar macrophages by in vitro inoculation" 110 : 207-219, 2006

15 Sabat R, "IL-10 family of cytokines" 21 : 315-324, 2010

16 Rovira A, "Experimental inoculation of conventional pigs with porcine reproductive and respiratory syndrome virus and porcine circovirus 2" 76 : 3232-3239, 2002

17 Pang VF, "Experimental T-2 toxicosis in swine following inhalation exposure: effects on pulmonary and systemic immunity, and morphological changes" 15 : 308-319, 1987

18 Li J, "Effects of porcine circovirus type 2 on expression of mRNA associated with endogenous antigen processing and presentation in pulmonary alveolar macrophages and circulating T lymphocytes in piglets" 193 : 199-205, 2012

19 Ellis JA, "Effect of coinfection with genogroup 1 porcine torque teno virus on porcine circovirus type 2-associated postweaning multisystemic wasting syndrome in gnotobiotic pigs" 69 : 1608-1614, 2008

20 Shi KC, "Cytokine mRNA expression profiles in peripheral blood mononuclear cells from piglets experimentally co-infected with porcine reproductive and respiratory syndrome virus and porcine circovirus type 2" 140 : 155-160, 2010

21 Darwich L, "Cytokine mRNA expression profiles in lymphoid tissues of pigs naturally affected by postweaning multisytemic wasting syndrome" 84 : 2117-2125, 2003

22 Chang HW, "Bacterial lipopolysaccharide induces porcine circovirus type 2 replication in swine alveolar macrophages" 115 : 311-319, 2006

23 Mandrioli L, "Apoptosis and proliferative activity in lymph node reaction in postweaning multisystemic wasting syndrome (PMWS)" 97 : 25-37, 2004

24 Duan D, "Activation of the TLR/MyD88/NF-B signal pathway contributes to changes in IL-4 and IL-12 production in piglet lymphocytes infected with porcine circovirus type 2 in vitro" 9 : e97653-, 2014

25 Lv Y, "Activation of NF-κB contributes to production of pig-major acute protein and serum amyloid A in pigs experimentally infected with porcine circovirus type 2" 95 : 1235-1240, 2013