Impaired Recovery from Influenza A/X-31(H3N2) Infection in Mice with 8-Lipoxygenase Deficiency

Lipoxygenase-derived lipid mediators can modulate inflammation and are stimulated in response to influenza infections. We report an effect of 8-lipoxygenase (ALOX8) on the recovery of mice after infection with Influenza virus X31. We compared the responses of 3- and 6-month-old mice with a deletion of ALOX8 (ALOX8−/−) to influenza infections with those of age-matched littermate wild-type mice (ALOX8+/+). The duration of illness was similar in 3-month-old ALOX8−/− and ALOX8+/+ mice. However, the 6-month-old ALOX8−/− mice showed a prolonged state of illness compared with ALOX8+/+ mice, as evidenced by reduced body temperatures, reduced locomotor activities, and delayed weight recovery. Although residual viral RNA in the lungs at day 10 post-inoculation was significantly influenced by the age of the ALOX8−/− mice, there were no significant differences between ALOX8−/− and ALOX8+/+ mice within the same age groups. The levels of cytokines interleukin 6 (IL-6) and keratinocyte chemoattractant (KC) differed significantly between 6-month-old ALOX8−/− and ALOX8+/+ mice 10 days after viral inoculation. Our data suggest that ALOX8 deficiency in mice leads to impaired recovery from influenza infection in an age-dependent manner

TRPC3 Is Dispensable for β-Alanine Triggered Acute Itch

Abstract The detection of pruritic (itchy) stimuli is mediated by a variety of receptors and channels expressed by primary sensory neurons. The G protein-coupled receptor (GPCR) MRGPRD is selectively expressed by a subset of mouse non-peptidergic nociceptors and functions as the molecular receptor for the itch-inducing chemical β-alanine. However, the channels responsible for generating electrical signals downstream of MRGPRD remain unclear. Here, we found that a member of the canonical TRP channel family, TRPC3, is highly expressed in MRGPRD+ non-peptidergic nociceptors, raising the possibility of whether TRPC3 functions as a downstream channel in the MRGPRD signaling pathway. We tested TrpC3 null mice for β-alanine induced itch, and found that these mice exhibit normal responses to β-alanine. At the cellular level, calcium influx triggered by β-alanine is also unchanged in cultured DRG neurons from TrpC3 null mice compared to wild type. Together, our results demonstrate that mouse TrpC3 is dispensable for β-alanine-induced acute itch

Pain and itch coding mechanisms of polymodal sensory neurons

Summary: Pain and itch coding mechanisms in polymodal sensory neurons remain elusive. MrgprD+ neurons represent a major polymodal population and mediate both mechanical pain and nonhistaminergic itch. Here, we show that chemogenetic activation of MrgprD+ neurons elicited both pain- and itch-related behavior in a dose-dependent manner, revealing an unanticipated compatibility between pain and itch in polymodal neurons. While VGlut2-dependent glutamate release is required for both pain and itch transmission from MrgprD+ neurons, the neuropeptide neuromedin B (NMB) is selectively required for itch signaling. Electrophysiological recordings further demonstrated that glutamate synergizes with NMB to excite NMB-sensitive postsynaptic neurons. Ablation of these spinal neurons selectively abolished itch signals from MrgprD+ neurons, without affecting pain signals, suggesting a dedicated itch-processing central circuit. These findings reveal distinct neurotransmitters and neural circuit requirements for pain and itch signaling from MrgprD+ polymodal sensory neurons, providing new insights on coding and processing of pain and itch