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Background Here, we describe a case of an intracranial fungal granuloma in an adult, non-castrated female dromedary camel ( Camelus dromedarius ). Case presentation An 11-year-old female dromedary presented with progressive neurological signs over several weeks. Neurological examination suggested a forebrain lesion, and magnetic resonance imaging (MRI) revealed a mass in the frontal fossa. Owing to poor prognosis, the animal was euthanized. Histopathological examination demonstrated a granulomatous-necrotizing inflammatory process containing fungal structures. Broad-range polymerase chain reaction (PCR) and amplicon sequencing results were consistent with a member of the Aspergillus fumigatus species complex being the causative agent. Conclusions Central nervous system involvement is rare in fungal infections. Intracranial fungal granulomas should be considered as a differential diagnosis in camels presenting with progressive neurological signs and space-occupying intracranial lesions.

Tuberculosis (TB) is a worldwide zoonotic disease caused by bacteria members of the Mycobacterium tuberculosis complex (MTC), which affects a wide range of domestic and wildlife species, as well as humans. TB is characterized as a chronic pulmonary infection, primarily affecting the lungs and local lymph nodes (LNs), causing significant respiratory and immunosuppression problems. MTC members have the capability to survive in the host by evading the immune system’s killing mechanisms and persisting within macrophages. This chronic antigenic stimulation promotes the formation of a complex, organized tissue structure known as a tuberculous granuloma, which is a defining cellular response to mycobacteria infections, and is composed of a compact aggregate of immune cells, whose functions are modulated by cytokines. The immune response against TB is complex and nowadays is not completely understood; therefore, the study of its immunopathogenesis becomes essential for evaluating immune-mediated response against mycobacterial infections, and consequently, develop strategies to control and eradicate the propagation of this disease in animals and humans. The aim of this work was to review the literature on key cell populations and immunological markers involved in the formation and development of granulomas in the lungs of humans and animals, and to discuss their potential use in evaluating the efficacy of novel vaccine candidates ‒ a tool that could contribute to TB control.

AbstractLactococcus garvieae is a significant pathogen in aquaculture with a potential zoonotic risk. To begin to characterize the late immune response of trout to lactococcosis, we selected infected individuals showing clinical signs of lactococcosis. At the time lactococcosis clinical signs appeared, infection by L. garvieae induced a robust inflammatory response in the spleen of rainbow trout, which correlated with abundant granulomatous lesions. The response in kidney goes in parallel with that of spleen, and most of the gene regulations are similar in both organs. A correlation existed between the early inflammatory granulomas in spleen (containing macrophages with internalized L. garvieae) and up-regulated gene sets, which defined the presence of macrophages and neutrophils. This is the first analysis of the immune transcriptome of rainbow trout following L. garvieae infection during the initiation of adaptive immune mechanisms and shows a transcriptome induction of antibody response by both IgM (+) and IgT (+) spleen B cells to respond to systemic infection. These results increase our understanding of lactococcosis and pave the way for future research to improve control measures of lactococcosis on fish farms.

Abstract Background Eosinophilic lung disease is a poorly understood inflammatory airway disease that results in substantial morbidity. Objective To describe clinical findings in dogs with eosinophilic lung disease defined on the basis of radiographic, bronchoscopic, and bronchoalveolar lavage fluid (BAL) analysis. Categories included eosinophilic bronchitis (EB), eosinophilic granuloma (EG), and eosinophilic bronchopneumopathy (EBP). Animals Seventy-five client owned dogs. Methods Medical records were retrospectively reviewed for dogs with idiopathic BAL fluid eosinophilia. Information abstracted included duration and nature of clinical signs, bronchoscopic findings, and laboratory data. Thoracic radiographs were evaluated for the pattern of infiltrate, bronchiectasis, and lymphadenomegaly. Results Thoracic radiographs were normal or demonstrated a bronchial pattern in 31 dogs assigned a diagnosis of EB. Nine dogs had intraluminal mass lesions and were bronchoscopically diagnosed with EG. The remaining 35 dogs were categorized as having EBP based on radiographic changes, yellow green mucus in the airways, mucosal changes, and airway collapse. Age and duration of cough did not differ among groups. Dogs with EB were less likely to have bronchiectasis or peripheral eosinophilia, had lower total nucleated cell count in BAL fluid, and lower percentage of eosinophils in BAL fluid compared to dogs in the other 2 groups. In contrast to previous reports, prolonged survival (>55 months) was documented in dogs with EG. Conclusions and Clinical Importance Dogs with eosinophilic lung disease can be categorized based on imaging, bronchoscopic and BAL fluid cytologic findings. Further studies are needed to establish response to treatment in these groups.

Background Sterile granuloma/pyogranuloma syndrome (SGPS) is an immune-mediated disease producing nodular and plaque-like skin lesions in dogs. Ocular involvement has been reported mainly in periocular skin and eyelids, with no histologically documented conjunctival lesions. This report describes a palpebral conjunctival nodule in a dog with SGPS and its distinction from nodular ocular surface diseases such as nodular granulomatous episcleritis and other differential diagnoses. Case presentation A 3-year-10-month-old Polish Tatra Dog presented with mucopurulent discharge, hyperaemia of the bulbar, palpebral, and third-eyelid conjunctivae, a firm 1 cm nodule on the right lower palpebral conjunctiva, and medial eyelid thickening with ectropion. Three months earlier, multiple cutaneous nodules had been diagnosed as SGPS. Topical and systemic corticosteroid therapy improved the skin lesions but neither the conjunctival mass nor the eyelid thickening, necessitating surgical excision of the nodule. In contrast, the eyelid thickening resolved during a subsequent prednisone taper, and no recurrence was observed over 20 months. Histopathology revealed a well-demarcated conjunctival stromal nodule with deep extension into the palpebral stroma, surrounding blood vessels, peripheral nerves, and the orbicularis oculi muscle. The infiltrate consisted of CD3⁺ T cells, CD20⁺/CD79⁺ B cells, plasma cells, MAC387-positive macrophages, and scattered Iba1-positive histiocytes, with small neutrophilic foci and no epithelioid cells, multinucleated giant cells, mitotic figures, or foreign material. Conclusion This case represents the first histopathologically confirmed conjunctival manifestation of SGPS. Its conjunctival origin and mixed lymphocytic–histiocytic profile expand the recognized spectrum of SGPS and support including SGPS in the differential diagnosis for well-circumscribed conjunctival nodules. Surgical excision may be required when such lesions do not regress or cause mechanical dysfunction.

Mycobacterium orygis, a member of the Mycobacterium tuberculosis complex (MTBC), has emerged as a significant contributor to tuberculosis (TB) in cattle, wildlife, and humans. However, understanding about its pathogenesis and severity is limited, compounded by the lack of reliable TB biomarkers in cattle. This study delves into the comparative pathology and transcriptomic landscape of pulmonary granulomas in cattle naturally infected with M. orygis, using high-throughput RNA sequencing. Histopathological analysis revealed extensive, multistage granulomatous, necrotic, and cavitary lesions, indicative of severe lung pathology induced by M. orygis. Transcriptomic profiling highlighted numerous differentially expressed genes and dysregulated pathways related to immune response modulation and extracellular matrix remodelling. Additionally, cell type enrichment analysis provided insights into the multicellularity of the granulomatous niche, emphasising complex cell-cell interactions within TB granulomas. Via comparative transcriptomics leveraging publicly available bovine and human TB omics datasets, 14 key immunomodulators (SOD2, IL1α/β, IL15, IL18, CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL8/MCP-2, CCL20/MIP-3α, CXCL2/MIP-2, CXCL10/IP-10, CXCL11, and IFN-γ) were identified as potential biomarkers for active TB in cattle. These findings significantly advance our understanding of M. orygis pathogenesis in bovine TB and highlight potential targets for the development of diagnostic tools for managing and controlling the disease.

Aluminum (Al) has been an effective adjuvant in vaccines for nearly a century in animals and humans. Al can induce persistent granulomatous inflammatory responses characterized by macrophages with large granular, blue-gray cytoplasm sometimes with intracytoplasmic structures known as crystalloid bodies. These granulomas have been linked to proliferative and neoplastic conditions at injection sites in animal and humans. The detection of Al in tissue is crucial but current methods are time-intensive and require specialized training. This study highlights the efficacy of the modified Al-hematoxylin (MAH) technique in animals. Tissues from Al-induced lesions in sheep and cats were examined, along with non-aluminum granulomas as controls and MAH results were confirmed with lumogallion staining. In sheep, MAH positively stained granuloma macrophages, crystalloid bodies, necrotic regions and nearby connective tissue macrophages, while lymphoid aggregates present in granulomas were consistently negative. Macrophages loaded with Al and crystalloid bodies in lymph nodes were also MAH-positive, as were macrophages in contaminated injection sites following application of commercial Al-based vaccines. In cats with Feline Injection Site Sarcoma (FISS), MAH detected macrophage clusters around the tumor periphery and within the sarcoma. This cost-effective, rapid, and specific technique provides valuable insights for diagnosing Al-related conditions and could serve as an animal model for other species, including humans.

Nasal granuloma in cattle results from inflammation within, and attendant proliferation of, the nasal mucosa possibly in response to an allergic response. However, the relationship between nasal granuloma and allergies remains unclear. Furthermore, severe cases have a poor prognosis because there is currently no effective treatment. Herein, we report three cases of nasal granuloma with severe stertorous breathing that were treated surgically. We also conducted an allergological exploration. Following surgical removal clinical signs did not recur in two of the three cases; however, stertorous breathing persisted in one case, and the cow was sacrificed 4 months later. A histopathological examination revealed that all nasal granulomas featured varying infiltrations of macrophages eosinophils, mast cells, and lymphocytes. The number of mast cells and the proportion of these cells that had degranulated were significantly higher in the granulomas than in normal nasal mucosae. In addition, serum histamine levels were higher in nasal granuloma cases than in normal cows, although serum immunoglobulin E levels were similar, and lymphocyte infiltration in the submucosal layer suggested type I and type IV allergies. Collectively, the results indicate the efficacy of complete surgical curettage for the treatment of allergic nasal granuloma in cattle. Further studies are required to identify the causes and risk factors of allergic nasal granuloma in cows.

Neurocysticercosis (NCC), a parasitic brain infection caused by Taenia solium larvae, remains a leading cause of preventable epilepsy globally. Although calcified brain lesions were formerly considered as the quiescent end stage of NCC, they may act as epileptogenic foci. It has been suggested that parasitic antigens within calcified lesions may act as potential triggers of inflammation and subsequent seizure activity. In this study, we developed and optimized immunohistochemistry (IHC) assays employing anti-Taenia solium monoclonal antibodies (mAbs) to detect residual cyst antigens in calcified lesions in a porcine NCC model and assessed antigen persistence for up to 12 months after successful antiparasitic treatment. Six mAbs raised against T. solium whole cyst (TsW5, TsW8, and TsW12), vesicular fluid (TsV3 and TsV4), and excretory/secretory products (TsE1) were used for IHC assay development and tested in brain sections containing viable brain cysts from NCC pigs and uninfected tissue from controls to optimize assay conditions, blocking, primary and secondary antibody dilutions. Optimized assays were subsequently performed in selected calcified granulomas (n = 20) obtained from NCC-infected pigs sacrificed at 4, 8, and 12 months after antiparasitic treatment to identify residual cyst antigens as well as their localization and area of reactivity. We observed residual cyst antigens in 65-80% of calcified granulomas, with TsW8 and TsV3 showing the highest percentages of immunoreactivity. Antigen localization followed two patterns, one with antigens entirely located within the calcified lesions (TsW5, TsW8, TsW12, and Tsv4) and another with antigens located outside the cyst in the perilesional brain tissue (TsV3 and TsE1). Antigen detection and the extent of reactivity declined progressively after antiparasitic treatment but persisted at detectable immunoreactive areas in calcified granulomas up to month 12 months after treatment. T. solium antigens remain detectable in calcified granulomas and in the perilesional tissue for up to 12 months after antiparasitic treatment in the pig model.

Bovine tuberculosis is a chronic inflammatory disease that causes granuloma formation. Characterization of granulomatous lesions of Mycobacterium bovis (M. bovis) experimentally infected cattle has helped to better understand the pathogenesis of this disease. However, few studies have described granulomas found in M. bovis naturally infected cattle. The aim of this work was to examine granulomas from Holstein-Friesian cattle naturally infected with M. bovis from a dairy basin located in the central region of Mexico. Tissue samples from thirty-two cattle with lesions suggestive of tuberculosis were collected post-mortem. Fifteen of the 32 sampled animals (46.8%) were 4 months of age or younger (calves), whereas the rest (53.2%, 17/32) were over one year old (adults). Macroscopic lesions suggestive of tuberculosis were found in the mediastinal lymph node chain of all animals (32/32). From the 1,143 granulomatous lesions that were microscopically analyzed, 34.6% (396/1143) were collected from adult animals and subsequently classified according to the nomenclature suggested by Wangoo et al., 2005. Surprisingly, lesions from calf tissues showed an atypical pattern which could not be fitted into the established developmental stages of this classification. Granulomatous lesions found in calves covered most of the affected organ, histologically showed large necrotic areas with central calcification, absence of a connective tissue capsule, and few giant cells. Also, there was a higher percentage of lesions with acid-fast bacilli (AFB) when compared to studied granulomas in adults. Growth of Mycobacterium spp was detected in 11 bacteriological tissue cultures. Genotypic identification of M. bovis was performed by DNA extraction from bacterial isolates, formalin-fixed and paraffin-embedded (FFPE) tissues and samples without bacterial isolation. M. bovis was detected by PCR in 84.3% (27/32) of the studied cases; whereas other AFB were observed in tissues of the remaining sampled animals (5/32). Our results describe atypical granuloma formation in calves 4 months of age or younger, naturally infected with M. bovis. These findings contribute to better understanding the physiopathology of M. bovis infection in cattle.