Feline infectious peritonitis (FIP), a fatal disease in cats worldwide, is caused by FCoV infection, which commonly occurs in multicat environments. The enteric FCoV, referred to as feline enteric virus (FECV), is considered a mostly benign biotype infecting the gut, whereas the FIP virus biotype is considered the highly pathogenic etiologic agent for FIP. Current laboratory tests are unable to distinguish between virus biotypes of FCoV. FECV is highly contagious and easily spreads in multicat environments; therefore, the challenges to animal shelters are tremendous. This review summarizes interdisciplinary current knowledge in regard to virology, immunology, pathology, diagnostics, and treatment options in the context of multicat environments.

Inflammation and immunoregulatory cytokines play a central role in alcohol-induced liver damage. We previously reported that acute alcohol treatment augments IL-10 and inhibits TNF-α production in monocytes. Heme oxygenase-1 (HO-1), a stress-inducible protein, also regulates IL-10 and TNF-α production. Here, we report that augmentation of LPS-induced IL-10 production by alcohol was prevented by inhibition of HO-1 activity. Acute ethanol increased LPS-induced enzyme activity and RNA levels of HO-1, and DNA binding of AP-1, a transcription factor essential in HO-1 regulation. LPS-induced phospho-p38 MAPK levels were augmented by ethanol treatment and the p38 inhibitor, SB203580, prevented both the ethanol-induced increase in IL-10 production and the inhibitory effect of ethanol on TNF-α production. Ethanol-induced down-regulation of TNF-α production was abrogated by inhibition of HO-1. We found that LPS-induced activation of NF-κB, a regulator of TNF-α, was inhibited by both ethanol treatment and HO-1 activation, but the ethanol-induced inhibition of NF-κB was HO-1 independent. In LPS-challenged mice in vivo, both acute alcohol administration and HO-1 activation augmented IL-10 and inhibited TNF-α serum levels. These results show that 1) acute alcohol augments HO-1 activation in monocytes, 2) HO-1 activation plays a role in alcohol-induced augmentation of IL-10 production likely via increased p38 MAPK activation, and 3) HO-1 activation is involved in attenuation of TNF-α production by alcohol independent of inhibition of NF-κB activation by alcohol. Thus, HO-1 activation is a key mediator of the anti-inflammatory effects of acute alcohol on monocytes.

Lipopolysaccharide (LPS) triggers cytokine production through Toll-like receptor 4 (TLR4), which shares downstream signaling pathways with TLR2. We investigated the roles of TLR2 and TLR4 in Propionibacterium acnes (P. acnes)-primed, LPS-induced liver damage using selective TLR ligands. Stock LPS induced interleukin 8 in both TLR4-and TLR2-expressing human embryonic kidney (HEK) 293 cells. Purified LPS (TLR4 ligand) activated HEK/TLR4 cells, while peptidoglycan and lipoteichoic acid (TLR2 ligands) activated HEK/TLR2 cells, respectively. In mice, P. acnes priming resulted in increased liver messenger RNA (mRNA) and serum levels of tumor necrosis factor ␣, interleukin 12, and interferon ␥ (IFN-␥) by both stock LPS and purified LPS challenges compared with nonprimed controls. In contrast, P. acnes failed to sensitize to TLR2 ligands (peptidoglycan ؉ lipoteichoic acid). In the liver, P. acnes-priming was associated with up-regulation of TLR4 and MD-2 proteins, and subsequent LPS challenge further increased MD-2 and CD14 mRNA levels. The lack of sensitization to TLR2 ligands by P. acnes correlated with no increase in hepatic TLR1 or TLR6 mRNA. In vitro, P. acnes pretreatment desensitized RAW macrophages to a secondary stimulation via both TLR2 and TLR4. However, IFN-␥ could selectively prevent desensitization to TLR4 but not to TLR2 ligands. Furthermore, P. acnes induced production of IFN-␥ in vivo as well as in isolated splenocytes. In vitro, P. acnes-primed Hepa 1-6 hepatocytes but not RAW macrophages produced increased MD-2 and CD14 mRNA levels after an LPS challenge. In conclusion, P. acnes priming to selective TLR4-mediated liver injury is associated with up-regulation of TLR4 and MD-2 and is likely to involve IFN-␥ and prevent TLR4 desensitization by P. acnes. (HEPATOLOGY 2004;40:555-564.)

Canine Atopic Dermatitis (AD) is a common complex and multifactorial disease involving immune dysregulation, genetic predisposition, skin barrier defects, environmental factors and allergic sensitization. To date, diagnosis of canine AD relies on a combination of patient history, clinical examination, allergy testing and response to diet trials/therapies with no reliable biomarkers available to distinguish AD from other diseases with similar clinical presentations. A handful of studies to identify potential biomarkers in the peripheral blood of AD dogs and healthy controls have been performed with some showing inconsistent and contradictory results. In this study, we, for the first time, report statistically significant increases in expression of phosphodiesterase 4D (PDE4D) gene in peripheral blood mononuclear cells (PBMCs) and miR-203 in plasma from AD dogs compared to healthy controls. In addition, we report a statistically non-significant change of the CD4 + /CD8 + ratio, a dramatic decrease of three gene markers (PIAS1, RORA and SH2B1) as well as a panel of differential expression of cytokines in AD dogs in comparison to the healthy controls. Our study provides important insight into the complexities of canine AD, and further studies to verify the specificity of these findings for canine AD at a larger-scale are warranted.

The concept of successional trajectories describes how small differences in initial community composition can magnify through time and lead to significant differences in mature communities. For many animals, the types and sources of early-life exposures to microbes have been shown to have significant and long-lasting effects on the community structure and/or function of the microbiome. In modern commercial poultry production, chicks are reared as a single age cohort and do not directly encounter adult birds. This scenario is likely to initiate a trajectory of microbial community development that is significantly different than non-industrial settings where chicks are exposed to a much broader range of environmental and fecal inocula; however, the comparative effects of these two scenarios on microbiome development and function remain largely unknown. In this work, we performed serial transfers of cecal material through multiple generations of birds to first determine if serial transfers exploiting the ceca in vivo, rather than the external environment or artificial incubations, can produce a stable microbial community. Subsequently, we compared microbiome development between chicks receiving this passaged, i.e. host-selected, cecal material orally, versus an environmental inoculum, to test the hypothesis that the first exposure of newly hatched chicks to microbes determines early GI microbiome structure and may have longer-lasting effects on bird health and development. Cecal microbiome dynamics and bird weights were tracked for a two-week period, with half of the birds in each treatment group exposed to a pathogen challenge at 7 days of age. We report that: i) a relatively stable community was derived after a single passage of transplanted cecal material, ii) this cecal inoculum significantly but ephemerally altered community structure relative to the environmental inoculum and PBS controls, and iii) either microbiome transplant administered at day-of-hatch appeared to have some protective effects against pathogen challenge relative to uninoculated controls. Differentially abundant taxa identified across treatment types may inform future studies aimed at identifying strains associated with beneficial phenotypes.