Up-regulation of pro-inflammatory factors by HP-PRRSV infection in microglia: Implications for HP-PRRSV neuropathogenesis

Chen, Xinxin; Quan, Rong; Guo, Xue-Kun; Gao, Li; Shi, Jishu; Feng, Wen-hai

doi:10.1016/j.vetmic.2014.01.031

Cited by 36 publications

(24 citation statements)

References 54 publications

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“…Reactive oxygen species represent an important component of the antimicrobial repertoire of macrophages and have been suggested as apoptosis mediators for PRRSV infected cells (Lee andKleiboeker, 2007 andYin et al, 2012). Reactive oxygen species up-regulation was also detected in microglia infected with PRRSV, and their production increased the inflammatory response of these cells on the cytokine level (Chen et al, 2014). Results of the present study confirmed that PRRSV can increase oxidative stress in PAMs (Fig.…”

Section: Discussionsupporting

confidence: 84%

Immune response of porcine alveolar macrophages to a concurrent infection with porcine reproductive and respiratory syndrome virus and Haemophilus parasuis in vitro

Kavanová

Prodělalová

Nedbalcová

et al. 2015

Veterinary Microbiology

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Section: Discussionsupporting

confidence: 84%

Immune response of porcine alveolar macrophages to a concurrent infection with porcine reproductive and respiratory syndrome virus and Haemophilus parasuis in vitro

Kavanová

Prodělalová

Nedbalcová

et al. 2015

Veterinary Microbiology

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“…Interestingly, the development of an encephalitic reaction following intranasal CA/09 infection occurred without breach of the BBB or T-cell infiltration into the brain parenchyma. Based on these results, we hypothesized that the increase in the number of microglia with activated morphology were, at least in part, secondarily attributable to the decrease in the intrinsically expressed neurotrophic factors [ 46 ] and the increased expression levels of circulating cytokines known to be involved with macrophage signaling following infections [ 47 , 48 ]. These could come from cytokine/chemokines released from T- and B-cells as well as endothelial cells in blood vessels lining the BBB [ 49 – 51 ].…”

Section: Discussionmentioning

confidence: 99%

Induction of Microglia Activation after Infection with the Non-Neurotropic A/CA/04/2009 H1N1 Influenza Virus

et al. 2015

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Although influenza is primarily a respiratory disease, it has been shown, in some cases, to induce encephalitis, including people acutely infected with the pandemic A/California/04/2009 (CA/09) H1N1 virus. Based on previous studies showing that the highly pathogenic avian influenza (HPAI) A/Vietnam/1203/2004 H5N1 virus was neurotropic, induced CNS inflammation and a transient parkinsonism, we examined the neurotropic and inflammatory potential of the CA/09 H1N1 virus in mice. Following intranasal inoculation, we found no evidence for CA/09 H1N1 virus neurotropism in the enteric, peripheral or central nervous systems. We did, however, observe a robust increase in microglial activity in the brain characterized by an increase in the number of activated Iba-1-positive microglia in the substantia nigra (SN) and the hippocampus, despite the absence of virus in the brain. qPCR analysis in SN tissue showed that the induction of microgliosis was preceded by reduced gene expression of the neurotrophic factors bdnf, and gdnf and increases in the immune modulatory chemokine chemokine (C-C motif) ligand 4 (ccl4). We also noted changes in the expression of transforming growth factor-1 (tgfβ1) in the SN starting at 7 days post-infection (dpi) that was sustained through 21 dpi, coupled with increases in arginase-1 (arg1) and csf1, M2 markers for microglia. Given that neuroinflammation contributes to generation and progression of a number of neurodegenerative disorders, these findings have significant implications as they highlight the possibility that influenza and perhaps other non-neurotropic viruses can initiate inflammatory signals via microglia activation in the brain and contribute to, but not necessarily be the primary cause of, neurodegenerative disorders.

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“…At PD7, pigs were inoculated intranasal with either 1 mL of sterile saline or 1 mL of 1 × 10 5 50% tissue culture infected dose (TCID50) of live PRRSV (strain P129-BV), obtained from the School of Veterinary Medicine at Purdue University (West Lafayette, Indiana). PRRSV, a single-stranded RNA virus, infects mononuclear myeloid cells in the lungs inducing an interstitial pneumonia (Chen et al, 2014; Duan et al, 1997). Rectal temperature and feeding score (0 = no attempt to consume the milk; 1 = attempted to consume the milk, but did not finish within 1 min; 2 = consumed all of the milk within 1 min) were determined daily beginning PD2.…”

Section: Methodsmentioning

confidence: 99%

Peripheral viral infection induced microglial sensome genes and enhanced microglial cell activity in the hippocampus of neonatal piglets

Schachtschneider

Schook

et al. 2016

Brain, Behavior, and Immunity

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Although poorly understood, early-life infection is predicted to affect brain microglial cells, making them hypersensitive to subsequent stimuli. To investigate this, we assessed gene expression in hippocampal tissue obtained from a previously published study reporting increased microglial cell activity and reduced hippocampal-dependent learning in neonatal piglets infected with porcine reproductive and respiratory syndrome virus (PRRSV), a virus that induces interstitial pneumonia. Infection altered expression of 455 genes, of which 334 were up-regulated and 121 were down-regulated. Functional annotation revealed that immune function genes were enriched among the up-regulated differentially expressed genes (DEGs), whereas calcium binding and synaptic vesicle genes were enriched among the down-regulated DEGs. Twenty-six genes encoding part of the microglia sensory apparatus (i.e., the sensome) were up-regulated (e.g. IL1R1, TLR2, and TLR4), whereas 15 genes associated with the synaptosome and synaptic receptors (e.g. NPTX2, GABRA2, and SLC5A7) were down-regulated. As the sensome may foretell microglia reactivity, we next inoculated piglets with culture medium or PRRSV at PD 7 and assessed hippocampal microglia morphology and function at PD 28 when signs of infection were waning. Consistent with amplification of the sensome, microglia from PRRSV piglets had enhanced responsiveness to chemoattractants, increased phagocytic activity, and secreted more TNFα in response to lipopolysaccharide and Poly I:C. Immunohistochemical staining indicated PRRSV infection increased microglia soma length and length-to-width ratio. Bipolar rod-like microglia not evident in hippocampus of control piglets, were present in infected piglets. Collectively, this study suggests early-life infection alters the microglia sensome as well as microglial cell morphology and function.

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Up-regulation of pro-inflammatory factors by HP-PRRSV infection in microglia: Implications for HP-PRRSV neuropathogenesis

Cited by 36 publications

References 54 publications

Immune response of porcine alveolar macrophages to a concurrent infection with porcine reproductive and respiratory syndrome virus and Haemophilus parasuis in vitro

Immune response of porcine alveolar macrophages to a concurrent infection with porcine reproductive and respiratory syndrome virus and Haemophilus parasuis in vitro

Induction of Microglia Activation after Infection with the Non-Neurotropic A/CA/04/2009 H1N1 Influenza Virus

Peripheral viral infection induced microglial sensome genes and enhanced microglial cell activity in the hippocampus of neonatal piglets

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