Novel Insights to Assess Climate Resilience in Goats Using a Holistic Approach of Skin-Based Advanced NGS Technologies.

A novel study was conducted to elucidate heat-stress responses on a number of hair- and skin-based traits in two indigenous goat breeds using a holistic approach that considered a number of phenotypic and genomic variables. The two goat breeds, Kanni Aadu and Kodi Aadu, were subjected to a simulated heat-stress study using the climate chambers. Four groups consisting of six goats each (KAC, Kaani Aadu control; KAH, Kanni Aadu heat stress; KOC, Kodi Aadu control; and KOH, Kodi Aadu heat stress) were considered for the study. The impact of heat stress on caprine skin tissue along with a comparative assessment of the thermal resilience of the two goat breeds was assessed. The variables considered were hair characteristics, hair cortisol, hair follicle quantitative PCR (qPCR), sweating (sweating rate and active sweat gland measurement), skin histometry, skin-surface infrared thermography (IRT), skin 16S rRNA V3-V4 metagenomics, skin transcriptomics, and skin bisulfite sequencing. Heat stress significantly influenced the hair fiber characteristics (fiber length) and hair follicle qPCR profile (Heat-shock protein 70 (HSP70), HSP90, and HSP110). Significantly higher sweating rate, activated sweat gland number, skin epithelium, and sweat gland number (histometry) were observed in heat stressed goats. The skin microbiota was also observed to be significantly altered due to heat stress, with a relatively higher alteration being noticed in Kanni Aadu goats than in Kodi Aadi goats. Furthermore, the transcriptomics and epigenetics analysis also pointed towards the significant impact of heat stress at the cellular and molecular levels in caprine skin tissue. The higher proportion of differentially expressed genes (DEGs) along with higher differentially methylated regions (DMRs) in Kanni Aadu goats due to heat stress when compared to Kodi Aadu goats pointed towards the better resilience of the latter breed. A number of established skin, adaptation, and immune-response genes were also observed to be significantly expressed/methylated. Additionally, the influence of heat stress at the genomic level was also predicted to result in significant functional alterations. This novel study thereby highlights the impact of heat stress on the caprine skin tissue and also the difference in thermal resilience exhibited by the two indigenous goat breeds, with Kodi Aadu goats being more resilient.

Intravenous immunoglobulin suppresses the polarization of both classically and alternatively activated macrophages.

Intravenous immunoglobulin (IVIG) is one of the widely used immunotherapeutic molecules in the therapy of autoimmune and inflammatory diseases. Previous reports demonstrate that one of the anti-inflammatory actions of IVIG implicates suppression of macrophage activation and release of their inflammatory mediators. However, macrophages are highly plastic and depending on the microenvironmental signals, macrophages can be polarized into pro-inflammatory classic (M1) or anti-inflammatory alternative (M2) type. This plasticity of macrophages raised additional questions on the role of IVIG towards macrophage polarization. In the present report, we show that IVIG affects the polarization of both classically and alternatively activated macrophages and this process is F(ab')2-independent. Our data thus indicate the lack of reciprocal regulation of inflammatory and non-inflammatory macrophages by IVIG.

Inhibition of MEK-ERK1/2-MAP kinase signalling pathway reduces rabies virus induced pathologies in mouse model.

The extracellular signal-regulated kinase (ERK) pathway has been shown to regulate pathogenesis of many viral infections, but its role during rabies virus (RV) infection in vivo is not clear. In the present study, we investigated the potential role of MEK-ERK1/2 signalling pathway in the pathogenesis of rabies in mouse model and its regulatory effects on pro-inflammatory cytokines and other mediators of immunity, and kinetics of immune cells. Mice were infected with 25 LD50 of challenge virus standard (CVS) strain of RV by intracerebral (i.c.) inoculation and were treated i.c. with U0126 (specific inhibitor of MEK1/2) at 10 µM/mouse at 0, 2, 4 and 6 days post-infection. Treatment with U0126 resulted in delayed disease development and clinical signs, increased survival time with lesser mortality than untreated mice. The better survival of inhibitor-treated and RV infected mice was positively correlated with reduced viral load and reduced viral spread in the brain as quantified by real-time PCR, direct fluorescent antibody test and immunohistochemistry. CVS-infected/mock-treated mice developed severe histopathological lesions with increased Fluoro-Jade B positive degenerating neurons in brain, which were associated with higher levels of serum nitric oxide, iNOS, TNF-α, and CXCL10 mRNA. Also CVS-infected/U0126-treated mice revealed significant decrease in caspase 3 but increase in Bcl-2 mRNA levels and less TUNEL positive apoptotic cells. CVS-infected/U0126-treated group also showed significant increase in CD4+, CD8+ T lymphocytes and NK cells in blood and spleen possibly due to less apoptosis of these cells. In conclusion, these data suggest that MEK-ERK1/2 signalling pathway play critical role in the pathogenesis of RV infection in vivo and opens up new avenues of therapeutics.