title: Peripheral viral infection induced microglial sensome genes and enhanced microglial cell activity in the hippocampus of neonatal piglets.
abstract: 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.
authors.affiliation: Department of Animal Sciences, University of Illinois, Urbana, IL, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Ji
authors.affiliation: Department of Animal Sciences, University of Illinois, Urbana, IL, USA; Animal Breeding and Genomics Center, Wageningen University, Wageningen, The Netherlands.
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Schachtschneider
authors.affiliation: Department of Animal Sciences, University of Illinois, Urbana, IL, USA; Institute for Genomic Biology, University of Illinois, Urbana, IL, USA.
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Schook
authors.affiliation: School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, Australia.
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Walker
authors.affiliation: Department of Animal Sciences, University of Illinois, Urbana, IL, USA; Division of Nutritional Sciences, University of Illinois, Urbana, IL, USA. Electronic address: rwjohn@illinois.edu.
authors.forename: Rodney W
authors.initials: RW
authors.lastname: Johnson
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D015870:Gene Expression; D020869:Gene Expression Profiling; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D017628:Microglia / Q000378:metabolism / Q000502:physiology* / Q000821:virology*; D019318:Porcine Reproductive and Respiratory Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D019316:Porcine respiratory and reproductive syndrome virus / Q000302:isolation & purification; D013552:Swine; D059467:Transcriptome / Q000235:genetics
chemical_list: D016207:Cytokines
keywords: Hippocampus; Infection; Microglia; Perinatal; Sensome; Synapse