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Gossypol, a secondary metabolite found in cotton (Gossypium spp.), is known to be toxic to a variety of animals, particularly monogastric mammals and commercial poultry (Gallus domesticus). Gossypol toxicosis in poultry include reduced weight, decreased egg production, and egg yolk discolouration. However, there is limited published data regarding gossypol toxicity in northern bobwhites (Colinus virginianus), which may encounter cottonseed products in the environment and subsequently ingest gossypol. We determined the oral LD50 of gossypol in northern bobwhites following the Environmental Protection Agency's OCSPP 850.2100 Guideline: Avian Acute Oral Toxicity Test. Through a range-finding test, we estimated that the LD50 was between 200 and 1,000 mg/kg body weight (BW). Following the range-finding test, we administered a single oral dose of refined gossypol to quail at 262, 342, 447, 585, and 765 mg/kg BW. We observed quail daily for mortality and any signs of intoxication throughout a 14-day observation period. We performed gross necropsies and had histopathology done on select organ tissues from experimental animals. Using the probit analysis, we determined that the oral LD50 of gossypol in northern bobwhites is 651 mg/kg BW (95% CI 579–731). Hepatocellular pigment accumulation and pancreatic necrosis were important lesions interpreted as evidence of gossypol toxicity. [ABSTRACT FROM AUTHOR]

Influenza viruses cause seasonal epidemics and sporadic pandemics, and are a major burden on human health. To develop better countermeasures and improve influenza disease outcomes, a clearer understanding of influenza pathogenesis is necessary. Host genetic factors have emerged as potential regulators of human influenza disease susceptibility, and in the mouse model, genetic background has been clearly linked to influenza pathogenicity. Here, we show that C57BL/6J mice are significantly more susceptible to disease caused by a 2009 pandemic H1N1 virus, an H7N9 virus, and a highly pathogenic H5N1 influenza virus compared to the closely related substrain, C57BL/6NJ. Mechanistically, influenza virus infection in C57BL/6J mice results in earlier presentation of edema, increased immune cell infiltration, higher levels of inflammatory cytokines, greater tissue damage, and delayed activation of regenerative processes in infected lung tissues compared to C57BL/6NJ mice. These differences are not dependent on virus replication levels. Six genes with known coding region differences between C57BL/6J and C57BL/6NJ strains exhibit increased transcript levels in influenza virus-infected mouse lungs, suggesting potential contributions to regulation of disease susceptibility. This work uncovers a previously unappreciated difference in disease susceptibility between the closely related C57BL/6J and C57BL/6NJ mice, which may be exploited in future studies to identify host factors and/or specific genetic elements that regulate host-dependent inflammatory mechanisms involved in influenza virus pathogenicity. [ABSTRACT FROM AUTHOR]

CD8+ cytotoxic T lymphocytes (CTLs) are critical for clearing many viral infections, and protective CTL memory can be induced by vaccination with attenuated viruses and vectors. Non-replicating vaccines are typically potentiated by the addition of adjuvants that enhance humoral responses, however few are capable of generating CTL responses. Adjuplex is a carbomer-lecithin-based adjuvant demonstrated to elicit robust humoral immunity to non-replicating antigens. We report that mice immunized with non-replicating Adjuplex-adjuvanted vaccines generated robust antigen-specific CTL responses. Vaccination by the subcutaneous or the intranasal route stimulated systemic and mucosal CTL memory respectively. However, only CTL memory induced by intranasal vaccination was protective against influenza viral challenge, and correlated with an enhancement of memory CTLs in the airways and CD103+ CD69+ CXCR3+ resident memory-like CTLs in the lungs. Mechanistically, Myd88-deficient mice mounted primary CTL responses to Adjuplex vaccines that were similar in magnitude to wild-type mice, but exhibited altered differentiation of effector cell subsets. Immune potentiating effects of Adjuplex entailed alterations in the frequency of antigen-presenting-cell subsets in vaccine draining lymph nodes, and in the lungs and airways following intranasal vaccination. Further, Adjuplex enhanced the ability of dendritic cells to promote antigen-induced proliferation of naïve CD8 T cells by modulating antigen uptake, its intracellular localization, and rate of processing. Taken together, we have identified an adjuvant that elicits both systemic and mucosal CTL memory to non-replicating antigens, and engenders protective CTL-based heterosubtypic immunity to influenza A virus in the respiratory tract. Further, findings presented in this manuscript have provided key insights into the mechanisms and factors that govern the induction and programming of systemic and protective memory CTLs in the respiratory tract. [ABSTRACT FROM AUTHOR]

Objective To describe five cases of protozoal keratitis or conjunctivitis in dogs with chronic preexisting ocular surface disease treated with long-term immunosuppression. Animals studied Five dogs that developed corneal or conjunctival mass lesions. Procedures The database of the Comparative Ocular Pathology Laboratory of Wisconsin was searched for canine cases diagnosed with corneal or conjunctival protozoal infection. Five cases were identified, and tissues were examined using routine and special histochemical stains: immunohistochemical labels for Neospora caninum, Toxoplasma gondii, and Leishmania spp., and tissue sample PCR for Leishmania spp. , Trypanosoma cruzi, tissue coccidia (i.e., T. gondii/Sarcocystis/Neospora), piroplasms, trichomonads, and Acanthamoeba. Electron microscopy was performed for two cases, and serology for N. caninum and T. gondii was available for three cases. Results Preexisting ocular diseases included keratoconjunctivitis sicca and pigmentary keratitis ( n = 4) and pyogranulomatous meibomian adenitis ( n = 1). All dogs were treated with tacrolimus or cyclosporine for at least 1.2 years. Dogs were presented with fleshy corneal or conjunctival masses that were clinically suspected to be neoplastic ( n = 4) or immune mediated ( n = 1). Histologic examination revealed granulomatous inflammation with intralesional protozoal organisms. Amoeba ( n = 2), T. gondii ( n = 2), or Leishmania mexicana ( n = 1) were identified using molecular techniques. Serological tests were negative. Conclusions Protozoal keratitis and conjunctivitis without systemic involvement appears rare and may be associated with chronic preexisting ocular surface disease treated with long-term immunosuppression. Based upon clinical appearance, lesions could be confused with neoplasia. This is the first report of amoebic keratoconjunctivitis in dogs and of L. mexicana in dogs in the United States. [ABSTRACT FROM AUTHOR]