Imaging diagnosis: CT characteristics of a retrobulbar hibernoma in a dog.

A 12-year-old female spayed Beagle was referred for investigation of exophthalmos. CT revealed a well-defined, retrobulbar mass causing rostro-dorsal displacement of the left globe. The mass had a mildly heterogeneous precontrast soft tissue attenuation with mild heterogeneous enhancement following iohexol administration. The mass was surgically removed en bloc with an orbital exenteration. Histopathology confirmed the mass to be a hibernoma, a benign tumor of brown adipose tissue. Hibernomas have CT characteristics consistent with both benign and malignant adipose tumors and may be underrecognized by radiologists.

Rapport de cas Ossifying fibroma in the cervical vertebra of a dog.

The objective of this study was to describe the clinical signs, neurologic examination findings, diagnostic imaging results, and pathologic diagnosis of ossifying fibroma in the cervical vertebra of a dog. A 3-year-old spayed female Pembroke Welsh corgi dog exhibited severe cervical pain and left-sided postural reaction deficits. Magnetic resonance imaging (MRI) revealed a lobulated contrast enhancing mass associated with the C6 cervical vertebra. Due to the lack of response to pain medications, humane euthanasia was elected, and histopathologic evaluation of the mass revealed a fibro-osseous lesion most consistent with an ossifying fibroma. This neoplasm is most commonly associated with the mandible of young horses and has not been previously reported in vertebrae in veterinary medicine. Key clinical message: This case is the first report of a fibro-osseous lesion most consistent with an ossifying fibroma affecting a vertebra in veterinary medicine.

Fibrome ossifiant dans la vertèbre cervicale d'un chien. Décrire les signes cliniques, les résultats de l'examen neurologique, les résultats de l'imagerie diagnostique et le diagnostic pathologique du fibrome ossifiant dans la vertèbre cervicale d'un chien. Une chienne Pembroke Welsh corgi femelle stérilisée âgée de 3 ans présentait de fortes douleurs cervicales et des déficits de réaction posturale du côté gauche. L'imagerie par résonance magnétique (IRM) a révélé une masse lobulée augmentant le contraste associée à la vertèbre cervicale C6. En raison de l'absence de réponse aux analgésiques, l'euthanasie a été choisie et l'évaluation histopathologique de la masse a révélé une lésion fibro-osseuse plus compatible avec un fibrome ossifiant. Ce néoplasme est le plus souvent associé à la mandibule des jeunes chevaux et n'a jamais été signalé auparavant dans les vertèbres en médecine vétérinaire.Message clinique clé :Ce cas est le premier rapport d'une lésion fibro-osseuse plus compatible avec un fibrome ossifiant touchant une vertèbre en médecine vétérinaire.(Traduit par Dr Serge Messier).

What Is Your Diagnosis?

In collaboration with the American College of Veterinary Radiology.

Superinfection with SARS-CoV-2 Has Deleterious Effects on Mycobacterium bovis BCG Immunity and Promotes Dissemination of Mycobacterium tuberculosis.

An estimated one-third of the world's population is infected with Mycobacterium tuberculosis, with the majority being vaccinated with Mycobacterium bovis BCG. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remains a threat, and we must understand how SARS-CoV-2 can modulate both BCG immunity and tuberculosis pathogenesis. Interestingly, neither BCG vaccination nor tuberculosis infection resulted in differences in clinical outcomes associated with SARS-CoV-2 in transgenic mice. Surprisingly, earlier M. tuberculosis infection resulted in lower SARS-CoV-2 viral loads, mediated by the heightened immune microenvironment of the murine lungs, unlike vaccination with BCG, which had no impact. In contrast, M. tuberculosis-infected tissues had increased bacterial loads and decreased histiocytic inflammation in the lungs following SARS-CoV-2 superinfection. SARS-CoV-2 modulated BCG-induced type 17 responses while decreasing type 1 and increasing type 2 cytokines in M. tuberculosis-infected mice. These findings challenge initial findings of BCG's positive impact on SARS-CoV-2 infection and suggest potential ramifications for M. tuberculosis reactivation upon SARS-CoV-2 superinfection. IMPORTANCE Prior to SARS-CoV-2, M. tuberculosis was the leading infectious disease killer, with an estimated one-third of the world's population infected and 1.7 million deaths a year. Here, we show that SARS-CoV-2 superinfection caused increased bacterial dissemination in M. tuberculosis-infected mice along with immune and pathological changes. SARS-CoV-2 also impacted the immunity of BCG-vaccinated mice, resulting in decreased interleukin-17 (IL-17) levels, while offering no protective effect against SARS-CoV-2. These results demonstrate that SARS-CoV-2 may have a deleterious effect on the ongoing M. tuberculosis pandemic and potentially limit BCG's efficacy.

Characterization of early immune responses elicited by live and inactivated vaccines against Johne's disease in goats.

Mycobacterium avium subspecies paratuberculosis (M. paratuberculosis) is the causative agent of Johne's disease, a chronic debilitating condition affecting ruminants causing significant economic losses to the dairy industry. Available inactivated vaccines are not effective in controlling the disease and vaccinated animals can continue to infect newly born calves. Recently, we have shown that a live-attenuated vaccine candidate (pgsN) is protective in goats and calves following challenge with virulent strains of M. paratuberculosis. To decipher the dynamics of the immune responses elicited by both live-attenuated and inactivated vaccines, we analyzed key immunological parameters of goats immunized through different routes when a marker-less pgsN vaccine was used. Within a few weeks, the inactivated vaccine triggered the formation of granulomas both at the site of inoculation and in regional lymph nodes, that increased in size over time and persisted until the end of the experiment. In contrast, granulomas induced by the pgsN vaccine were small and subsided during the study. Interestingly, in this vaccine group, histology demonstrated an initial abundance of intra-histiocytic mycobacterial bacilli at the site of inoculation, with recruitment of very minimal T lymphocytes to poorly organized granulomas. Over time, granulomas became more organized, with recruitment of greater numbers of T and B lymphocytes, which coincided with a lack of mycobacteria. For the inactivated vaccine group, mycobacterial bacilli were identified extracellularly within the center of caseating granulomas, with relatively equal proportions of B- and T-lymphocytes maintained across both early and late times. Despite the differences in granuloma-specific lymphocyte recruitment, markers for cell-mediated immunity (e.g., IFN-γ release) were robust in both injected pgsN and inactivated vaccine groups. In contrast, the intranasal live-attenuated vaccine did not elicit any reaction at site of inoculation, nor cell-mediated immune responses. Finally, 80% of animals in the inactivated vaccine group significantly reacted to purified protein derivatives from M. bovis, while reactivity was detected in only 20% of animals receiving pgsN vaccine, suggesting a higher level of cross reactivity for bovine tuberculosis when inactivated vaccine is used. Overall, these results depict the cellular recruitment strategies driving immune responses elicited by both live-attenuated and inactivated vaccines that target Johne's disease.

Pathology in Practice.

In collaboration with the American College of Veterinary Pathologists.

Transcriptome analysis of human monocytic cells infected with Burkholderia species and exploration of pentraxin-3 as part of the innate immune response against the organisms.

BACKGROUND: Burkholderia mallei (Bm) is a facultative intracellular bacterial pathogen causing highly-fatal glanders in solipeds and humans. The ability of Bm to thrive intracellularly is thought to be related to exploitation of host immune response-related genes and pathways. Relatively little is known of the molecular strategies employed by this pathogen to modulate these pathways and evade intracellular killing. This manuscript seeks to fill gaps in the understanding of the interface between Bm and innate immunity by examining gene expression changes during infection of host monocytes. METHODS: The transcriptome of Bm-infected human Mono Mac-6 (MM6) monocytes was profiled on Affymetrix Human Transcriptome GeneChips 2.0. Gene expression changes in Bm-infected monocytes were compared to those of Burkholderia thailandensis (Bt)-infected monocytes and to uninfected monocytes. The resulting dataset was normalized using Robust Multichip Average and subjected to statistical analyses employing a univariate F test with a random variance model. Differentially expressed genes significant at p < 0.001 were subjected to leave-one-out cross-validation studies and 1st and 3rd nearest neighbor prediction model. Significant probe sets were used to populate human pathways in Ingenuity Pathway Analysis, with statistical significance determined by Fisher's exact test or z-score. RESULTS: The Pattern Recognition Receptor (PRR) pathway was represented among significantly enriched immune response-related human canonical pathways, with evidence of upregulation across both infections. Among members of this pathway, pentraxin-3 was significantly upregulated by Bm- or Bt-infected monocytes. Pentraxin-3 (PTX3) was demonstrated to bind to both Bt and Burkholderia pseudomallei (Bp), but not Bm. Subsequent assays did not identify a role for PTX3 in potentiating complement-mediated lysis of Bt or in enhancing phagocytosis or replication of Bt in human monocytes. CONCLUSION: We report on the novel binding of PTX3 to Bt and Bp, with lack of interaction with Bm, suggesting that a possible evasive mechanism by Bm warrants further exploration. We determined that (1) PTX3 may not play a role in activating the lytic pathway of complement in different bacterial species and that (2) the opsonophagocytic properties of PTX3 should be investigated in different primary or immortalized cell lines representing host phagocytes, given lack of binding of PTX3 to MM6 monocytes.

Melioidosis and glanders modulation of the innate immune system: barriers to current and future vaccine approaches.

Burkholderia pseudomallei and Burkholderia mallei are pathogenic bacteria causing fatal infections in animals and humans. Both organisms are classified as Tier 1 Select Agents owing to their highly fatal nature, potential/prior use as bioweapons, severity of disease via respiratory exposure, intrinsic resistance to antibiotics, and lack of a current vaccine. Disease manifestations range from acute septicemia to chronic infection, wherein the facultative intracellular lifestyle of these organisms promotes persistence within a broad range of hosts. This ability to thrive intracellularly is thought to be related to exploitation of host immune response signaling pathways. There are currently considerable gaps in our understanding of the molecular strategies employed by these pathogens to modulate these pathways and evade intracellular killing. A better understanding of the specific molecular basis for dysregulation of host immune responses by these organisms will provide a stronger platform to identify novel vaccine targets and develop effective countermeasures.