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An Acute Stress Model in New Zealand White Rabbits Exhibits Altered Immune Response to Infection with West Nile Virus.

ABSTRACT: The immune competence of an individual is a major determinant of morbidity in West Nile virus (WNV)-infection. Previously, we showed that immunocompetent New Zealand White rabbits (NZWRs; Oryctolagus cuniculus) are phenotypically resistant to WNV-induced disease, thus presenting a suitable model for study of virus-control mechanisms. The current study used corticosteroid-treated NZWRs to model acute "stress"-related immunosuppression. Maximal effects on immune parameters were observed on day 3 post dexamethasone-treatment (pdt). However, contrary to our hypothesis, intradermal WNV challenge at this time pdt produced significantly lower viremia 1 day post-infection (dpi) compared to untreated controls, suggestive of changes to antiviral control mechanisms. To examine this further, RNAseq was performed on RNA extracted from draining lymph node-the first site of virus replication and immune detection. Unaffected by dexamethasone-treatment, an early antiviral response, primarily via interferon (IFN)-I, and induction of a range of known and novel IFN-stimulated genes, was observed. However, treatment was associated with expression of a different repertoire of IFN-?-21-like and IFN-?-1-like subtypes on 1 dpi, which may have driven the different chemokine response on 3 dpi. Ongoing expression of Toll-like receptor-3 and transmembrane protein-173/STING likely contributed to signaling of the treatment-independent IFN-I response. Two novel genes (putative HERC6 and IFIT1B genes), and the SLC16A5 gene were also highlighted as important component of the transcriptomic response. Therefore, the current study shows that rabbits are capable of restricting WNV replication and dissemination by known and novel robust antiviral mechanisms despite environmental challenges such as stress.

SUBMITTER: Suen WW

PROVIDER: S-EPMC6963736 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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An Acute Stress Model in New Zealand White Rabbits Exhibits Altered Immune Response to Infection with West Nile Virus.

Suen Willy W WW Imoda Mitchell M Thomas Albert W AW Nasir Nur N B M NNBM Tearnsing Nawaporn N Wang Wenqi W Bielefeldt-Ohmann Helle H

Pathogens (Basel, Switzerland) 20191018 4

The immune competence of an individual is a major determinant of morbidity in West Nile virus (WNV)-infection. Previously, we showed that immunocompetent New Zealand White rabbits (NZWRs; <i>Oryctolagus cuniculus</i>) are phenotypically resistant to WNV-induced disease, thus presenting a suitable model for study of virus-control mechanisms. The current study used corticosteroid-treated NZWRs to model acute "stress"-related immunosuppression. Maximal effects on immune parameters were observed on ...[more]

PMID: 31635289

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Project description:BackgroundHeat stress (HS) disrupts the gut barrier allowing the uptake of lipopolysaccharide (LPS) and leads to an inflammatory response and changes in gut microbiota composition. Moringa oleifera leaf powder (MOLP) has been proposed to combat HS, yet its alleviate role is currently under investigation. The current study investigated the effects of chronic HS and MOLP supplementation on changes in redox status and immune response of cecal mucosa along with alteration in cecal microbiota.MethodsA total of 21 young New Zealand White (NZW) rabbits (male) about 32 weeks old (mean body weight of 3318 ± 171 g) reared on a commercial pelleted diet were employed; divided into three groups (n = 7): control (CON, 25 °C), heat stress (HS, 35 °C for 7 h daily), and HS supplemented orally with MOLP (HSM, 35 °C) at 200 mg/kg body weight per day for 4 weeks.ResultsThe results demonstrated that MOLP supplementation increased organ index of cecal tissue compared with the HS group (P > 0.05). Levels of malonaldehyde (MDA) and activity of superoxide dismutase (SOD) as well as lactate dehydrogenase (LDH) were reduced in the cecal mucosa of the HSM group compared with the HS group. MOLP downregulated the contents of cecal mucosa LPS, several inflammatory markers (TNF-α/IL-1α/IL-1β), and myeloperoxidase (MPO) in the HSM group (P < 0.05). Secretory immunoglobulin A (SIgA) was increased in the HSM group compared with the HS group (P < 0.05). The transcriptome of cecal mucosa showed that MOLP reduced gene expression relative to several immune factors, including IL-10, IFNG, and RLA, whereas both HS and MOLP increased the gene expression of fat digestion and absorption pathway, including APOA1, FABP1, FABP2, MTTP, and LOC100344166, compared to the CON group (P < 0.001). At the phylum level, the relative abundance of Proteobacteria was increased by HS, while Actinobacteria was significantly increased by HSM compared to other groups (P < 0.05). At genus level, Papillibacter was higher in abundance in HSM groups compared to CON and HS groups (P < 0.05). Higher butyrate concentrations were observed in the HSM group than HS and CON groups (P < 0.05).ConclusionIn conclusion, HS in growing rabbits resulted in alteration of cecal microbiota at phyla level as well as increased oxidative stress and expression of mucosal inflammatory genes. Whereas, oral MOLP supplementation elevated the relative weight of cecum, affected their immunological and cecal micro-ecosystem function by improving antioxidant status and down-regulating mucosal tissue inflammatory response.

Project description:BackgroundBuprenorphine is one of the most used analgesics for postoperative pain in rabbits. The recommended dose in rabbits (0.01-0.05 mg/kg) is the same for intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration, despite lack of pharmacokinetic data. Five male and five female New Zealand White rabbits (mean ± SD body weight 3.1 ± 0.3 kg) were administered 0.05 mg/kg buprenorphine by the IV, IM and SC routes and 0.1 mg/kg by the SC route, in a cross-over design with two-week wash-out periods between treatments. Blood was collected before, and up to 8 h post buprenorphine injection, for determination of serum levels by UPHLC-MS/MS.ResultsThe area under the time concentration curve (AUC0-t) was lower after SC (398 ± 155 ng/mL/min) than IM (696 ± 168 ng/mL/min, p < 0.001) and IV (789 ± 189 ng/mL/min, p < 0.001) administration. The maximum serum concentration was lower after SC (2.2 ± 1.4 ng/mL) than after IM (11 ± 3.2 ng/mL) administration (p < 0.001). The bioavailability was lower after SC (50 ± 19%) than after IM (95 ± 21%) administration (p = 0.006). The elimination half-life was longer after SC (260 ± 120 min) than after IM (148 ± 26 min, p = 0.002) as well as IV (139 ± 33 min) injection (p < 0.001). An increase in the SC dose from 0.05 to 0.1 mg/kg resulted in an increase in the area under the time concentration curve of 50% in female (p = 0.022) and 165% in male rabbits (p < 0.001). The bioavailability did not change in the females (36 ± 14%, p = 0.6), whereas it increased in the males (71 ± 23%, p = 0.008).ConclusionsThe lower bioavailability of 0.05 mg/kg buprenorphine after SC administration could explain the lack of efficacy seen in clinical pain studies in rabbits, using this route. For immediate pain relief, IV or IM administration is therefore be recommended, whereas SC administration may be useful to sustain analgesic serum levels, once efficient pain relief has been achieved. The current data do not support an increase in dose to compensate for the lower SC bioavailability.

Dataset Information

An Acute Stress Model in New Zealand White Rabbits Exhibits Altered Immune Response to Infection with West Nile Virus.

Publications

An Acute Stress Model in New Zealand White Rabbits Exhibits Altered Immune Response to Infection with West Nile Virus.

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