Severe Granulomatous Inflammation Research Articles

Matrix metalloproteinases inhibition reveals the association between inflammation, collagen accumulation and intestinal translocation of Schistosoma mansoni eggs in vivo

Schistosomiasis mansoni is a parasitic infection that causes enterohepatic morbidity associated with severe granulomatous inflammation triggered by parasite eggs. In this disease, granulomatous inflammation leads to intestinal erosion and environmental excretion of S. mansoni eggs from feces, an essential process for propagating the parasite and infecting host organisms. Metalloproteinases (MMP) are involved in S. mansoni-induced hepatic granulomatous inflammation and fibrosis. However, the relationship between MMP and collagen accumulation with the intestinal excretion of parasite eggs remains unclear. Thus, the present study investigated whether MMP inhibition is capable of modulating granulomatous inflammation, collagen accumulation and mechanical resistance to the point of influencing the dynamics between intestinal retention and excretion of S. mansoni eggs in infected mice. Our findings indicated that doxycycline (a potent MMP inhibitor) aggravates intestinal inflammation and subverts collagen dynamics in schistosomiasis. By attenuating MMP-2 and MMP-9 activity, this drug is capable of enhancing fibrosis and mechanical resistance of the intestinal wall, hindering S. mansoni eggs translocation. Although collagen content was not correlated with MMP activity, intestinal retention and fecal excretion of parasite eggs in untreated mice; these correlations were observed for doxycycline-treated animals. Thus, our study provides evidence that doxycycline is able to attenuate fecal elimination of S. mansoni eggs by inhibiting MMP-2 and MMP-9 activity, events potentially associated with excessive collagen accumulation, which increases intestinal mechanical resistance and hinders eggs translocation through the intestinal wall. Variations in intestinal collagen dynamics are relevant since they may represent changes in the environmental dispersion of S. mansoni eggs, bringing repercussions for schistosomiasis propagation.

Distribution of M1 and M2 macrophages in cerebral granulomas caused by Encephalitozoon cuniculi

Encephalitozoon cuniculi spores cause severe granulomatous inflammation in the brain where mononuclear cells and macrophages infiltrate. Here, we orally infected New Zealand white rabbits with 1 × 106E. cuniculi viable spores to study the recruitment and localization of macrophages in brain granulomas. At day 30 post-infection, the positive phenotype markers iNOS (M1) and Arg-1 (M2) were located in the periphery and center of granulomas, respectively. Live intracytoplasmic spores were found only in positive Arg-1 cells. This is the first work to describe the recruitment and distribution of M1 and M2 macrophages in the brain granulomas of rabbits infected with E. cuniculi.

Kudoa hypoepicardialis and associated cardiac lesions in invasive red lionfish Pterois volitans in Grenada, West Indies.

Invasive red lionfish Pterois volitans (Linnaeus, 1758) represent an ongoing ecological threat within temperate and tropical waters. Relatively little is known regarding the overall health of P. volitans and their potential for spreading pathogens in non-native regions. Lionfish collected from inshore reefs of Grenada, West Indies, in 2019 and 2021 were identified as P. volitans based on cytochrome c oxidase subunit 1 barcoding. Gross and microscopic examination of tissues revealed myxozoan plasmodia in the hearts of 24/76 (31.6%) lionfish by histopathology or wet mount cytology. Further histopathologic examination revealed severe granulomatous inflammation and myofiber necrosis associated with developing plasmodia and presporogonic life stages. Fresh myxospores were morphologically and molecularly consistent with Kudoa hypoepicardialis, being quadrate in apical view with 4 valves and 4 equal polar capsules. The spore body was 5.1-7.9 (mean: 6.0) µm long, 8.1-9.8 (8.7) µm wide, and 6.9-8.5 (7.7) µm thick. Polar capsules were 2.3-2.7 (2.5) µm long and 0.9-1.6 (1.3) µm wide. 18S small subunit rDNA sequences were 99.81-99.87% similar to sequence data from the original description of the species. Novel 28S large subunit rDNA and elongation factor 2 data, which did not match any previously reported species, were provided. This is the first account of a myxozoan parasite of P. volitans, a new host record and locality for K. hypoepicardialis, and one of few reports describing pathogen-associated lesions in invasive lionfish.

A Partially Protective Vaccine for Fasciola hepatica Induced Degeneration of Adult Flukes Associated to a Severe Granulomatous Reaction in Sheep.

Simple SummaryFasciolosis is a parasitic disease of livestock causing important economic losses worldwide and it is also a zoonosis. Current therapy relies on the use of anthelmintic drugs, which is no longer sustainable due to the increase of anthelmintic resistance and the risk of drug residues in food. A deep understanding of the host-parasite interaction is required to develop protective vaccines for the control of fasciolosis. The aim of the present study is to evaluate the hepatic lesions in sheep vaccinated with a partly protective vaccine for F. hepatica, a non-protective vaccine and an infected control group. The protective vaccine showed less severe hepatic lesions than the infected control group. In addition, in the protective vaccine group dead flukes surrounded by a severe granulomatous inflammation were observed, which taken together with the lower fluke burden, suggests that the host response induced by the partially protective vaccine may have been involved in the death of adult flukes of F. hepatica. This is the first study reporting the presence of degenerated flukes associated to a severe granulomatous inflammation in bile ducts in a vaccine trial, a finding that would be useful for improving vaccine efficacy in future trials.Fasciolosis is an important economic disease of livestock. There is a global interest in the development of protective vaccines since current anthelmintic therapy is no longer sustainable. A better knowledge of the host-parasite interaction is needed for the design of effective vaccines. The present study evaluates the microscopical hepatic lesions in sheep immunized with a partially protective vaccine (VAC1), a non-protective vaccine (VAC2), and an infected control group (IC). The nature of granulomatous inflammation associated with degeneration of adult flukes found in the VAC1 group was characterized by immunohistochemistry. Hepatic lesions (fibrous perihepatitis, chronic tracts, bile duct hyperplasia, infiltration of eosinophils and lymphocytes and plasma cells) were significantly less severe in the VAC1 group than in the IC group. Dead adult flukes within bile ducts were observed only in the VAC1 group and were surrounded by a severe granulomatous inflammation composed by macrophages and multinucleate giant cells with a high expression of lysozyme, CD163 and S100 markers, and a low expression of CD68. Numerous CD3+ T lymphocytes and scarce infiltrate of FoxP3+ Treg and CD208+ dendritic cells were present. This is the first report describing degenerated flukes associated to a severe granulomatous inflammation in bile ducts in a F. hepatica vaccine trial.

A Case History of Internal Ophthalmomyiasis, a Rare and Devastating Disease

To report a rare case of unilateral internal ophthalmomyiasis with complete visual loss. Method: An otherwise healthy 12 years old boy presented with redness and painful rapid loss of vision in his right eye for the past 12 days. There was no history of associated trauma. On examination, there was no perception of light in his right eye and normal vision in left eye. There was severe anterior and posterior segment inflammation which prevented the view of fundus. B-scan of the right eye showed diffuse choroidal and optic nerve thickening. Routine blood count and X-ray chest did not reveal any significant findings. In the midst of uncertainity regarding diagnosis and to relieve the patient from severe pain, enucleation of right eye was performed and histopathological examination of the specimen was done to confirm the diagnosis. Result: Histopathology report showed gross irregular inflammatory thickening of the choroid with severe granulomatous inflammation. There was an infective agent in the choroid having an outer cuticle and an irregular hyaline branching innner tube. These features were suggestive of ophthalmomyiasis of the choroid. Conclusion: Although rare, ophthalmomyiasis should be considered in the differential diagnosis of panuveitis. Early recognition of this condition, when tumour and other conditions are suspected, would avoid invasive surgical procedures, such as enucleation.

Intestinal Mycobacterium avium Infection in Pet Dwarf Rabbits (Oryctolagus cuniculus)

Mycobacteriosis has been rarely described in pet rabbits (Oryctolagus cuniculus). Here we present two cases of intestinal mycobacteriosis from north-eastern Germany. The first adult rabbit was euthanized due to severe cardiovascular failure, hypothermia and chronic weight loss. Necropsy revealed cachexia and a focal, fibrinonecrotic lesion in the caecum. Histologically, severe granulomatous inflammation, with numerous multinucleated giant cells and abundant acid-fast bacilli, was detected under the fibrinonecrotic material in the abdominal wall adjacent to the caecal lesion, caecal lymph nodes, spleen, liver and lungs. Microbiological culture detected Mycobacterium avium subspecies hominissuis, Escherichia coli, Clostridium disporicum and Bacteroides ovatus. A retrospective assessment of 2,013 other pet rabbit necropsies, performed between 1995 and 2019, revealed one additional case of intestinal mycobacteriosis. This animal had been euthanized due to persistent hindlimb lameness and necropsy revealed comminuted fractures of the pelvic bones and multiple large liquefied abscess-like lesions in the caecal and colonic walls. Histology revealed granulomatous inflammation with acid-fast bacilli. Polymerase chain reaction on formalin-fixed, paraffin-embedded tissue identified the presence of M. avium spp. In contrast to European wild rabbits (Oryctolagus cuniculus) from Scotland, these findings indicate that intestinal mycobacteriosis is rare in pet rabbits from north-eastern Germany. Zoonotic potential should be considered due to the close contact between pets and their owners and the chronic course of the disease with an initial lack of clinical signs.

First case report of fatal Nocardia nova infection in yellow-bibbed lory (Lorius chlorocercus) identified by multilocus sequencing

BackgroundNocardiosis is often a multi-systemic disease in humans and other mammals. Nocardiosis in birds is uncommon. Laboratory identification of Nocardia to the species level is difficult by traditional phenotypic methods based on biochemical reactions and hydrolysis tests, and is most accurately performed by sequencing multiple gene targets.Case presentationWe report the first case of fatal Nocardia nova infection in a yellow-bibbed lory nestling in an oceanarium diagnosed by multilocus sequencing. Necropsy examination showed effacement of normal sternal musculature with yellowish, firm aberrant material, and diffuse infiltration of the lungs with nodular, tan to yellow foci. Histologically, severe granulomatous inflammation with marked necrosis was observed in the lung, spleen and sternal musculature. Fine, sometimes Gram-positive, 0.5–1 μm wide, branching and beaded filamentous organisms were visible within the lesions. They were acid-fast on Fite-Faraco stain. Tissue samples obtained from the sternum, liver, right lung and right kidney recovered Nocardia species. Sequencing of four gene loci and phylogenetic analysis of concatenated (gyrB-16S-secA1-hsp65) sequences revealed that the isolate was N. nova.ConclusionsWe report the first case of N. nova infection in yellow-bibbed lorry (Lorius chlorocercus). The present case is the first one of which the species identity of the isolate was determined by multilocus sequencing. Molecular diagnosis is important for identifying the Nocardia to species level and understanding the epidemiology of nocardiosis in birds.

Neottialges (Caloenectes) vulturis (Dubinin, 1956) (Acari: Hypoderatidae) from the Eurasian griffon vulture (Gyps fulvus) in Italy: first record in Europe, redescription and pathological changes in the host

Deutonymphs of the astigmatan mite Neottialges (Caloenectes) vulturis (Dubinin, 1956) comb. n. (Astigmata: Hypoderatidae) were found during the anatomo-histopathological study of a Eurasian griffon vulture, Gyps fulvus, found dead in Central Italy. After skinning, numerous cystic formations were visible in the subcutaneous tissue of the vulture, each containing a parasitic mite. Microscopically, subcutaneous tissue showed large areas of severe granulomatous inflammation. To our knowledge, this is the first record of this poorly known hypoderatid mite in Europe, about five thousand kilometers west from the type locality in Kirghizstan. The deutonymphal stage of N. (C.) vulturis is redescribed following modern standards of taxonomic description for astigmatan mites. This mite, previously unassigned to a subgenus, is now placed in the subgenus Caloenectes Fain, 1966.

Histopathological findings in canine dirofilariosis

The lesions found in ten dogs with severe chronic dirofilariosis were studied. In the lungs, the most significant changes were observed in the endarterium of the pulmonary artery branches. Also, remarkable were the vascular thrombosis and the granulomatous inflammatory response of the pulmonary parenchyma. The presence of severe granulomatous inflammation in the endarterium of the pulmonary artery branches in one dog, is considered significant, because this finding has been reported only in cat In the liver, congestion, intravascular coagulation in the portal system and fibrosis were found. The severity of hepatic lesions was not correlated with the number of adult heartworms found in the posterior vena cava. The kidneys showed mild to moderate membranoproliferative glomerulonephritis and intravenus blood coagulation.

Sarcoidosis presenting as severe renin-dependent hypertension due to kidney vascular injury.

Renal sarcoidosis embraces a wide variety of clinical patterns. Renal vascular involvement has seldom been reported and usually in the setting of systemic vasculitis. We report the case of a 22-year-old patient in whom inaugural manifestation of renal sarcoidosis consisted of severe hypertension associated with bilateral perfusion defects and tumour-like nodules. In the setting of renal sarcoidosis, our case suggests that renin-dependant hypertension may arise from renal ischaemia as a result of extrinsic compression of kidney blood vessels due to severe granulomatous inflammation.

First description of Mycobacterium heckeshornense infection in a feline immunodeficiency virus-positive cat

A 13-year-old cat was presented to the veterinary clinic with poor condition, vomiting and a reduced appetite. A painful abdomen was diagnosed because of tension and defence reactions on palpation. Diagnostic laparotomy showed a thickening of the colon and caecal intestinal wall. Histopathological investigation of intestinal biopsies revealed focal severe granulomatous inflammation with numerous acid-fast bacilli in the tela submucosa. The complete blood count test showed a severe lymphopenia and anaemia, and the cat tested positive for feline immunodeficiency virus (FIV) antibodies by enzyme-linked immunosorbent assay. The cat was euthanased and necropsied. Multifocal granulomatous nodules were present in the intestines, liver and kidneys. The gastric lymph node was markedly enlarged and showed a caseous cut surface. Histopathology revealed a systemic mycobacteriosis affecting intestine, lymph nodes, liver and kidneys. The mycobacterial strain was cultured and determined by its unique 16S rRNA gene sequence as Mycobacterium heckeshornense. This is the first reported case of M heckeshornense in a cat. It was suspected that the disseminated mycobacteriosis was supported by the FIV infection.

Mirror, mirror on the wall: Hypercalcemia as a consequence of modern cosmetic treatment with liquid silicone

SummaryBackgroundHypercalcemia is a common problem in clinical practice and can be related to endocrine disorders or malignant disease, especially in elderly patients. Although rare, other causes can also be responsible.Case ReportGranulomatous inflammation of the skin and lymph nodes induced by intravenous or injectable silicone is a rare condition of hypercalcemia that is usually not within the scope of differential diagnosis. Here, we report a 72-year-old woman with symptomatic hypercalcemia related to cosmetic treatment of the neck. Topical applied liquid silicone by means of a focal ultrasound device induced extensive granulomatous inflammation of the skin and local lymph nodes, being the underlying cause for hypercalcemia in this case.ConclusionsIn rare cases, symptomatic hypercalcemia can be caused by silicone due to a severe granulomatous tissue reaction. This is the first time that a transdermal silicone treatment has been reported to cause severe granulomatous tissue inflammation.

Isolation ofMycobacterium aviumsubsp.paratuberculosisfrom Muscle Tissue of Naturally Infected Cattle

Johne's disease or paratuberculosis is a chronic granulomatous inflammation of the small intestine of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). Recent studies suggest an association between MAP and Crohn's disease in humans. MAP can become widely distributed within the tissues of infected animals, and meat may be a possible route of exposure of MAP to humans. In this study, 47 dairy and beef cattle were examined for the occurrence of viable MAP in diaphragm muscle. At the slaughterhouse, gut tissues, diaphragm muscle, blood, and feces of the 47 animals were collected for bacteriological culture, as well as gut samples for histopathological analysis. MAP was detected by bacteriological culture and conventional and real-time IS900 polymerase chain reaction in the diaphragm muscle of six infected cattle at slaughter (13%). The six animals showing evidence of MAP in diaphragm muscle had diffuse lesions and severe granulomatous inflammation in ileocecal lymph nodes, jejunal lymph nodes, ileocecal valve, and ileum. All six had heavy bacterial load in mesenteric lymph nodes, ileocecal valve, ileum, and jejunum, and four showed clinical signs of paratuberculosis. Two animals did not show clinical signs but had viable MAP in intestinal tissues and in diaphragm muscle as well. MAP was found in blood of only one of the six animals showing evidence of MAP in diaphragm muscle and in feces of three of them. In general, there was a positive association between enteric lesion severity, clinical signs of paratuberculosis, heavy bacterial load in intestinal tissues, fecal shedding of MAP, and the presence of disseminated MAP infection in diaphragm muscle. The results of this study demonstrated that MAP can be detected and cultured from muscle of MAP-infected cattle destined for human consumption and suggest a possible risk of exposure of humans to MAP via contaminated meat.

Distribution of the Inflammatory Lesions in the Central Nervous System of Dogs Affected with Disseminated and Ocular Form of Granulomatous Meningoencephalomyelitis

An aged Maltese dog (dog 1) showed gait ataxia for a month and suddenly died after convulsion. An aged Toy Poodle dog (dog 2) showed sudden blindness with unresponsive pupillary light reflexes and sudden death due to acute cardiac failure. Histological examination of the two dogs demonstrated severe granulomatous perivascular inflammation in the white matter throughout the central nervous system (CNS) including the brain and spinal cord. Based on the clinical and pathological findings, these dogs were diagnosed as granulomatous meningoencephalomyelitis (GME). In dog 2, the inflammatory changes predominated in the visual system such as the optic nerve, optic tract and optic radiation in the cerebrum (ocular form). Distribution pattern of the inflammatory lesions in the CNS was compared between the two dogs.

Transmission of tuberculosis between men and pet birds: a case report

The present report describes a case of Mycobacterium tuberculosis infection in an African Grey parrot (Psittacus erithacus erithacus) kept as a pet bird. Diagnosis was confirmed by microbiologic and pathologic results, and indicated a human–avian transmission. Clinical signs included sublingual nodules resulting in anorexia and signs of osteolysis in the long bones. Proliferation consisted of several nodules with small greenish-caseous foci in cross-section and revealed a severe granulomatous inflammation without intralesional acid-fast rods. M. tuberculosis was cultured from a pooled sample of sublingual and liver nodules, and was confirmed via polymerase chain reaction. Transmission between men and parrot was proved by spoligotyping pattern analysis. The absence of facial skin lesions and acid-fast rods within the tubercles is contrary to previous publications of tuberculosis in birds. This disease in a common pet bird species is of zoonotic importance, and those parrots with close contact to owners suffering from tuberculosis may serve as a potential reservoir for human infection.

Spinal Cryptococcoma in an Immunocompetent Cat

SummaryThis report describes an unusual case of primary cryptococcoma in the proximal thoracic spinal cord of an 11-year-old immunocompetent cat from a farm on which there were large numbers of pigeons. This animal was referred for examination with progressive paralysis and shown to be free from feline immunodeficiency virus, feline leukaemia virus, feline coronavirus and Toxoplasma gondii. It died 2 months later. At necropsy, the only lesion detected was a malacic area, 4 cm in length, in the spinal cord. Histopathological examination of the spinal cord revealed severe granulomatous inflammation associated with large numbers of encapsulated yeast cells. In addition to the granulomatous host response, necrosis, digestion chambers, Gitter cells, spheroids and lymphocytic perivascular cuffs were features of the malacic areas. Immunohistochemistry confirmed the presence of Cryptococcus neoformans var. grubii yeast cells.

Aneurysmata der Aorta ascendens und des Truncus pulmonalis

A case of two non-atherosclerotic aneurysms localised in the ascending aorta and in the pulmonary trunk is presented. Histopathologically, a severe granulomatous inflammation affecting the whole aneurysms wall was documented. To the best of our knowledge it is the second ever documented case of simultaneous occurrence of aneurysms in the aorta and the pulmonary artery.

Nitric oxide produced in Peyer's patches exhibits antiapoptotic activity contributing to an antimicrobial effect in murine salmonellosis

Salmonella species normally infect hosts via the oral-fecal route. We previously reported that NO had potent host defense functions in murine salmonellosis, not only via a direct antibacterial effect but also because it was cytoprotective for infected host cells. Here, we used an oral route to infect iNOS-deficient mice infected with S. enterica serovar Typhimurium to further investigate the cytoprotective role of NO in preventing damage caused by Salmonella organisms in PP. Oral bacterial challenge (2 x 10(5) CFU, or >100 LD(50)) produced a more severe infection and greater lethality in iNOS-deficient mice than in iNOS-competent mice. We used specific antibodies to S. enterica Typhimurium, neutrophils, iNOS, nitrotyrosine, and dendritic cells (CD11c-positive) in histochemical and immunohistochemical studies to examine infected PP tissues. S. enterica Typhimurium colonization in PP from iNOS-deficient mice was significantly higher than that in wild-type mice. Histochemical assays showed extensive cellular damage in PP. We then examined PP tissues for apoptosis by means of in situ TUNEL analysis and by measuring caspase-3 specific activity in tissue homogenates. Increased numbers of TUNEL-positive cells and severe granulomatous inflammation with increased infiltration of neutrophils and macrophages were observed during infection in iNOS-deficient mice compared with wild-type mice. iNOS-deficient mice had increased numbers of dendritic cells and significantly higher caspase-3-specific activity in PP. These data confirm that NO exerts its protective function not only through direct antibacterial action, but also by preventing apoptosis and thereby contributing to antimicrobial defense during salmonellosis.

Possible Human–Avian Transmission of Mycobacterium tuberculosis in a Green-Winged Macaw (Ara chloroptera)

This report describes a case of Mycobacterium tuberculosis infection in a green-winged macaw (Ara chloroptera), confirmed by microbiologic and pathologic diagnostics, and notes a possible human-avian transmission. Clinical signs included cutaneous swellings, profound leukocytosis, and signs of osteomyelitis in the long bones. Proliferation consisted of several nodules with small greenish-caseous foci in cross-section and revealed a severe granulomatous inflammation with intralesional acid-fast rods. Mycobacterium tuberculosis was isolated from subcutaneous nodules and biochemically confirmed. The disease in avian species is of zoonotic importance.

Granulomatous pyelitis associated with urinary obstruction: a comprehensive clinicopathologic study

Urinary obstruction is rarely associated with a distinct granulomatous inflammation, which involves the pyelocalyceal system and closely simulates infectious conditions including tuberculosis. Its clinicopathologic features, however, have not been adequately studied since there are only seven isolated reported cases. In a comprehensive study of 112 kidney specimens with urinary obstruction, we identified five cases of granulomatous pyelitis. The features of these cases were detailed and compared with the previously reported cases. Among the five identified subjects, three patients had history of urolithiasis and two had ureteral stenosis and all had stent placement 7 weeks to 12 years before nephrectomy for relief of the unilateral urinary obstruction. The age distribution was between 38 and 81 years. Two had end-stage renal disease or chronic renal failure. The pyelocaliceal system showed frank hydronephrosis (1 case) or partial dilatation (4 cases) and contained cheesy and gritty material in its lumen. Each case showed severe granulomatous inflammation, which was limited to the pelvic wall and closely associated with calcified debris, necrotic inflammatory cells, and material consistent with Tamm–Horsfall protein. The kidney showed chronic tubulointerstitial nephritis but without granulomas. Cultures of urine, blood, and the renal pelvic content, and special stains of tissue sections did not show fungi or mycobacteria in any case. Many of these features were also observed in previously reported cases. Granulomatous pyelitis is a rare but distinct cliniocopathologic entity characterized by severe noninfectious granulomatous inflammation limited to the renal pelvis, which is uniformely asociated with urinary obstruction and pyelocalyceal dilatation and may develop in response to accumulated calcified material in the renal pelvis. Awareness of this entity and its characteristic clinicopathologic features also helps eliminate an infectious etiology with obvious treatment and prognostic implications.