Development Of Granulomas Research Articles

A Case of Subcutaneous Sarcoidosis Treated With Intralesional Kenalog

Abstract Sarcoidosis is a granulomatous disorder that is characterized by the development of noncaseating granulomas affecting multiple organ systems, most commonly the lungs and lymph nodes of the body. Aside from these organ systems, sarcoidosis can also affect the skin, eyes, central nervous system, liver, heart, kidneys, and musculoskeletal system. We present a patient with subcutaneous sarcoidosis, also known as Darier-Roussy disease, without extracutaneous findings. Patients may benefit from topical or intralesional steroids for localized involvement to decrease the size of the nodules while avoiding the adverse effects of systemic medications.

Terpinolene inhibits acute responses triggered by different inflammatory agents in vivo models of mouse

The aim of this work was evaluate the effects of terpinolene on acute inflammatory responses in mice. In vivo preclinical research using different inflammatory agents to induce acute responses and evaluate the effects of terpinolene in orally treated mice. The acute inflammatory responses were induced by injecting phlogistic agents in the mice paw to observe the development of pain responses (formalin test) or edema (carrageenan, dextran, histamine, arachidonic acid, and prostaglandin). The antiedematogenic activity was also evaluated using a croton oil-induced ear edema model. Finally, cotton pellet-induced granuloma was used to carry out a preliminary evaluation of terpinolene in a chronic inflammatory model. Topically administered terpinolene (5, 10, and 20 mg/mL) significantly inhibited ear edema development (by 33.82%, 29.63%, and 33,30%, respectively). Following an oral administration, only the highest dose of the monoterpene (200 mg/kg) reduced the licking time of the formalin test in both phases 1 (73.55%) and 2 (96.61%). The carrageenan-induced edema significantly inhibited over time following the oral administration of terpinolene at 50 mg/kg (T1: 47.74%, T2: 54.67%, T3: 48.63%, and T4: 62.99%), 100 mg/kg (T1: 72.86%, T2: 71.03%, T3: 48.63%, and T4: 57.83%), and 200 mg/kg (T1: 43.22%, T2: 34.11%, T3: 36.47%, and T4: 45.20%). On the other hand, only the dose of 200 mg/kg) caused a significant reduction of the dextran-induced paw edema (T1: 51.18%, T2: 60%, T3: 50.92%, and T4: 65.15%). Regarding the participation of inflammatory pathways, the monoterpene (200 mg/kg, p.o.) had little impact on histamine-induced edema, while the edema induced by arachidonic acid was significantly reduced at all time-points (T1: 37.04%, T2: 24.32%, and T3: 35.13%, and T4: 35.53%), which was corroborated by the observation that the compound inhibited the response triggered by prostaglandin E2 (PGE2), suggesting interference with downstream signaling cascades. Finally, terpinolene (200 mg/kg, p.o.) reduced both the weight (21.43%) and total protein content (36.21%) of the cotton pellet-induced granuloma, indicating an anti-inflammatory activity in this chronic model. Terpinolene inhibited acute inflammatory responses and reduced granuloma development in vivo, possibly by interfering with the tissue changes orchestrated by inflammatory mediators such as histamine and PGE2. However, the molecular mechanisms underlying this pharmacological observation need to be confirmed by further research.

The role of the host gut microbiome in the pathophysiology of schistosomiasis.

The pathophysiology of schistosomiasis is linked to the formation of fibrous granulomas around eggs that become trapped in host tissues, particularly the intestines and liver, during their migration to reach the lumen of the vertebrate gut. While the development of Schistosoma egg-induced granulomas is the result of finely regulated crosstalk between egg-secreted antigens and host immunity, evidence has started to emerge of the likely contribution of an additional player-the host gut microbiota-to pathological processes that culminate with the formation of these tissue lesions. Uncovering the role(s) of schistosome-mediated changes in gut microbiome composition and function in granuloma formation and, more broadly, in the pathophysiology of schistosomiasis, will shed light on the mechanisms underlying this three-way parasite-host-microbiome interplay. Such knowledge may, in turn, pave the way towards the discovery of novel therapeutic targets and control strategies.

Symptoms: Purple Ear Drum and Hearing Loss

Symptoms: Purple Ear Drum and Hearing Loss

Review on the prevalence and economic importance of camel tuberculosis in Ethiopia

Camel tuberculosis is a chronic disease, which is portrayed by the development of granulomas, essentially in the respiratory tract and related lymph nodes, from which the mycobacteria are discharged and contaminate other susceptible animals. Camel tuberculosis has public health implications, especially in pastoral areas of Ethiopia due to the communities having the habit of consuming raw milk and its products and those who do have consistent or day-to-day contact with their camels. In the pastoral areas of Ethiopia, the camel is the spine of their everyday life and extraordinarily adjusted to cruel conditions camels are for the most part raised in Afar, Somali, and Oromia (Borena, Kereyu and Guji). Camels have a high contribution to the economic development of the country. The pastoral community utilized camel products, such as milk and meat, and used camels for various purposes for example, for transportation, drafting, ploughing land, festivity and rivalry as in dashing. In most parts of Ethiopia, camel milk is accepted as a treatment for gastritis, asthmatics, stomach inconvenience, HIV, Hamot (kar), tuberculosis, fever, urinary issues and hepatitis. Among significant illnesses, tuberculosis is one of the principles, which influence camel’s Health and has a zoonotic impact. In addition to this, the etiological agents are transmitted to humans through an aerogenous route from those animals with active cases in the herd. The infection has been reported from several parts of pastoral areas of the country essentially dependent on tuberculin tests and abattoir inspections. Therefore, attention should be given to the control of tuberculosis in livestock; public health education on the zoonotic importance of the disease or awareness creation and the national tuberculosis control needs to consider the one health approach and further epidemiological studies should be undertaken.

Evaluación de la incidencia, factores predictivos y consideraciones sobre el tratamiento de los granulomas genitourinarios asintomáticos después de la terapia intravesical con bacilo de Calmette-Guérin

Introduction and objectivesAlthough the complications of intravesical BCG treatment are well described, asymptomatic genitourinary granulomas after BCG therapy have rarely been reported and management strategy for these conditions remains controversial. The objective of this study is to evaluate the incidence rate of asymptomatic genitourinary granuloma formation mimicking bladder cancer recurrence after intravesical bacillus Calmette-Guérin (BCG) therapy and to identify the diagnostic and treatment strategies according to patient conditions. Patients and methodsA retrospective review was conducted on 162 patients who underwent intravesical BCG therapy. For patients who developed granulomas, we evaluated the time interval between BCG instillation and the development of granuloma, the presence of acid-fast bacteria on pathology specimens, culture/polymerase chain reaction results, management strategies for the lesions, and clinical outcomes. ResultsAsymptomatic genitourinary masses developed in 14 patients, of whom 5 underwent histological examinations and all were confirmed to have granulomatous inflammation. The affected organs included the kidney, bladder, prostate, and penis. While four of the five patients did not receive treatment for their granulomas, one patient was administered antituberculous medication to prevent worsening of the lesion during the perioperative period of the scheduled cystoprostatectomy. None of the patients experienced worsening or recurrence of granulomatous lesions. Patients who developed asymptomatic masses (n=14) were significantly younger than those who did not (P=.0076) and multivariate analysis also showed that younger age was independently associated with the development of clinically suspicious lesions (P=.032); however, none of the parameters were associated with histologically confirmed granuloma formation. ConclusionsGenitourinary granulomas mimicking recurrence of carcinoma may develop in nearly 10% of patients after intravesical BCG therapy. Most patients can be managed without potentially toxic antituberculosis therapy.

Evaluation of incidence, predictive factors and treatment considerations for asymptomatic genitourinary granulomas after intravesical bacillus Calmette-Guérin therapy

Introduction and objectivesAlthough the complications of intravesical BCG treatment are well described, asymptomatic genitourinary granulomas after BCG therapy have rarely been reported and management strategy for these conditions remains controversial. The objective of this study is to evaluate the incidence rate of asymptomatic genitourinary granuloma formation mimicking bladder cancer recurrence after intravesical bacillus Calmette-Guérin (BCG) therapy and to identify the diagnostic and treatment strategies according to patient conditions. Patients and methodsA retrospective review was conducted on 162 patients who underwent intravesical BCG therapy. For patients who developed granulomas, we evaluated the time interval between BCG instillation and the development of granuloma, the presence of acid-fast bacteria on pathology specimens, culture/polymerase chain reaction results, management strategies for the lesions, and clinical outcomes. ResultsAsymptomatic genitourinary masses developed in 14 patients, of whom 5 underwent histological examinations and all were confirmed to have granulomatous inflammation. The affected organs included the kidney, bladder, prostate, and penis. While four of the five patients did not receive treatment for their granulomas, one patient was administered antituberculous medication to prevent worsening of the lesion during the perioperative period of the scheduled cystoprostatectomy. None of the patients experienced worsening or recurrence of granulomatous lesions. Patients who developed asymptomatic masses (n = 14) were significantly younger than those who did not (p = 0.0076) and multivariate analysis also showed that younger age was independently associated with the development of clinically suspicious lesions (p = 0.032); however, none of the parameters were associated with histologically confirmed granuloma formation. ConclusionsGenitourinary granulomas mimicking recurrence of carcinoma may develop in nearly 10% of patients after intravesical BCG therapy. Most patients can be managed without potentially toxic antituberculosis therapy.

Vaccine-Induced Subcutaneous Granulomas in Goats Reflect Differences in Host-Mycobacterium Interactions between BCG- and Recombinant BCG-Derivative Vaccines.

Tuberculous granulomas are highly dynamic structures reflecting the complex host–mycobacterium interactions. The objective of this study was to compare granuloma development at the site of vaccination with BCG and its recombinant derivatives in goats. To characterize the host response, epithelioid cells, multinucleated giant cells (MNGC), T cell subsets, B cells, plasma cells, dendritic cells and mycobacterial antigen were labelled by immunohistochemistry, and lipids and acid-fast bacteria (AFB) were labelled by specific staining. Granulomas with central caseous necrosis developed at the injection site of most goats though lesion size and extent of necrosis differed between vaccine strains. CD4+ T and B cells were more scarce and CD8+ cells were more numerous in granulomas induced by recombinant derivatives compared to their parental BCG strain. Further, the numbers of MNGCs and cells with lipid bodies were markedly lower in groups administered with recombinant BCG strains. Microscopic detection of AFB and mycobacterial antigen was rather frequent in the area of central necrosis, however, the isolation of bacteria in culture was rarely successful. In summary, BCG and its recombinant derivatives induced reproducibly subcutaneous caseous granulomas in goats that can be easily monitored and surgically removed for further studies. The granulomas reflected the genetic modifications of the recombinant BCG-derivatives and are therefore suitable models to compare reactions to different mycobacteria or TB vaccines.

Sarcoid-like reaction in patients with malignant tumors: Long-term clinical course and outcomes.

BackgroundThe development of non-caseating epithelioid cell granulomas in cancer patients who do not fulfill the systemic sarcoidosis criteria is termed sarcoid-like reaction (SLR). Little is known about this condition's natural course and impact on the prognosis of malignancy. We aimed to investigate the natural course and prognostic value of cancer-associated SLR.MethodsClinical data were retrospectively analyzed in 32 patients with biopsy-proven cancer-associated SLR. Among patients with non-small cell lung cancer (NSCLC), SLR cases (n = 8) were matched with non-SLR cases (n = 78) for survival analysis.ResultsAmong the included patients, the mean age was 59.7 years, and 68.8% were female. The median follow-up period was 35.6 months [interquartile range (IQR): 14.0–61.4 months]. Of all the included malignancies (n = 32), breast cancer (25.0%) and NSCLC (25.0%) were the most common, with stage I being the most frequent tumor stage (59.4%). During follow-up, SLR progression to overt sarcoidosis was not observed. In the 28 patients with available follow-up computed tomography images (median interval: 24.9 months; IQR: 14.4–41.7), 4 patients received corticosteroids (n = 4), resulting to a decrease of SLR lesions. Meanwhile, among those who did not receive treatment (n = 24), the extent of SLR decreased or did not change in 85.7% of them, whereas 3.6% had increased SLR extent. Furthermore, among patients with NSCLC, SLR was not associated with overall survival [hazard ratio (HR) = 1.28, 95% confidence interval (CI): 0.02–67.71, P = 0.882] and recurrence of malignancy (HR = 1.27, 95% CI 0.21–7.51, P = 0.793) in the Cox proportional hazard regression model.ConclusionsDuring the follow-up of cancer-related SLR, we found no further evidence for systemic sarcoidosis, and most of the lesions decreased or did not change. Development of SLR was also not associated with overall survival or disease-free survival in patients with NSCLC.

Umbilical granuloma frequency of newborns in Third-line Hospital in Turkey.

The aim is to determine the umbilical granuloma frequency of newborns and etiological factors. In this study, the records of 21344 newborns who were admitted to our hospital between February 2015 and August 2019, were examined. 21191 newborns are included in the study. 2.4% of newborns was Syrian refugee and others were citizens of Turkey. Umbilical granuloma frequency was % 3.83. While umbilical granuloma frequency was 3.85% in Turkish citizen newborns, %3.01 in Syrians. Mean umbilical cord seperation time was 7.1 days in cases with umbilical granuloma. There was no statistically significant relationship determined between umbilical granuloma development and race and time of umbilical cord seperation (p >0.05) The frequency of umbilical granuloma was 3.5% for boys and 4.1% for girls. Umbilical granuloma was being observed statistically significantly higher in girls than in boys (p <0.05). 80.8% of the cases with umbilical granuloma were bathed before the umbilical cord seperation. A significant difference was determined between bathing before umbilical cord seperation and umbilical granuloma development (p < 0.05). Umbilical granuloma, with frequency of 3.83% in newborns. Umbilical granuloma is more common in girls and newborns bathed before the umbilical cord seperation.

Adenosine metabolized from extracellular ATP promotes type 2 immunity through triggering A2BAR signaling in intestinal epithelial cells.

SUMMARYIntestinal nematode parasites can cross the epithelial barrier, causing tissue damage and release of danger-associated molecular patterns (DAMPs) that may promote host protective type 2 immunity. We investigate whether adenosine binding to the A2B adenosine receptor (A2BAR) on intestinal epithelial cells (IECs) plays an important role. Specific blockade of IEC A2BAR inhibits the host protective memory response to the enteric helminth, Heligmosomoides polygyrus bakeri (Hpb), including disruption of granuloma development at the host-parasite interface. Memory T cell development is blocked during the primary response, and transcriptional analyses reveal profound impairment of IEC activation. Extracellular ATP is visualized 24 h after inoculation and is shown in CD39-deficient mice to be critical for the adenosine production mediating the initiation of type 2 immunity. Our studies indicate a potent adenosine-mediated IEC pathway that, along with the tuft cell circuit, is critical for the activation of type 2 immunity.

Development of cutaneous sarcoidosis to permanent eyebrow makeup procedure

The article summarizes the data on historical aspects, epidemiology, etiopathogenesis, clinical picture, diagnosis and treatment of skin sarcoidosis. Sarcoidosis is a chronic multisystem disease from the group of granulomatoses of unknown etiology, the morphological feature of which is the development of epithelioid cell granulomas without caseous necrosis with the processes of dystrophy, destruction and fibrosis in the tissues of various organs. Diagnosis and differential diagnosis of sarcoidosis are based on clinical examination, changes in laboratory data, X-ray methods and skin biopsy. The differential diagnosis includes many dermatoses, including tuberculoid type of leprosy, tuberculous lupus, lichen planus, annular granuloma, etc. In the treatment of sarcoidosis of the skin, corticosteroid drugs are used, including prolonged action. In case of resistance or contraindications, synthetic antimalarial and immunosuppressive agents are prescribed.&#x0D; According to the literature, cases of granulomatous reactions after permanent makeup procedures have become more frequent. The tattoo procedure is widespread and considered to be safe, but adverse reactions, particularly sarcoidosis of the skin, may develop.&#x0D; The etiology of sarcoidosis has been studied for more than 150 years and remains poorly understood until now. There are increasingly frequent reports in the literature about the development of immune granulomatous inflammation reactions after a numerous of cosmetic procedures, such as tattooing, botulinum toxin A injection, hyaluronic acid injections, permanent makeup, biorevitalization, facial modeling fillers, blepharoplasty. The increasing number of cases of skin sarcoidosis due to cosmetological manipulations is the subject of great scientific interest, and the growth of publications on this topic is an evidence of modern etiopathogenetic mechanisms of the disease development.&#x0D; Here is our clinical observation of skin sarcoidosis without systemic manifestations in a 54-year-old patient after permanent eyebrows make-up procedure outside the medical organization, without prior examination and lack of follow-up (the skin process is subacute; polymorphism of the rash is noted; rashes on the skin in the eyebrow area are represented by merging papules, foci correspond to the area of pigment injection). According to the results of physical, laboratory and instrumental studies, many epithelioid cell granulomas without caseous necrosis were found. The patient received a course of intraocular pricking with a prolonged glucocorticoid drug (Betamethasone suspension, No. 5), which led to a complete regression of rashes. Recommendations for the removal of pigment are given.&#x0D; In order to prevent infection and minimize the risks of complications, a high level of qualification of a dermatocosmetologist working in a specialized medical institution is a prerequisite for permanent makeup.

LB902 Treatment outcomes for silicone granuloma: A systematic review

Injectable silicone has been used for body contouring and enhancement, particularly but not exclusively in transgender women. Large-volume silicone injections are often complicated by the development of silicone granulomas that form over months to years, resulting in pain and disfiguration. To our knowledge, no evidence-based guidelines exist for the treatment of silicone granulomas. This systematic review aimed to characterize treatments and associated outcomes for silicone granuloma. The review protocol was registered with PROSPERO (#CRD42021260380) and was reported in accordance with PRISMA guidelines. We searched PubMed/MEDLINE, Cochrane Library, EMBASE, and Web of Science on 6/4/2021 for observational studies or clinical trials published in English reporting treatment outcomes for silicone injected-based cosmetic foreign-body reactions. We included 98 studies (95 case reports/series, 3 cross-sectional), with 239 total patients (28.5% male, 67.4% female, and 4.2% unknown gender). Patients underwent surgical removal (n=148), systemic therapy (41), multiple modalities (37), laser (6), injection (5), and topical treatments (1). Surgical removal led to complete response in 57/148 (39%) and partial response in 87/148 (59%). Outcomes for systemic steroids led to complete response in 4/19 (21%), partial response in 10/19 (53%), and stable disease in 4/19 (21%). Intralesional triamcinolone or 5-fluorouracil injections led to partial response in 3/5 (60%). Multiple modalities, including combinations of systemic, surgical, and injection options, led to complete response in 9/37 (24%) and partial response in 22/37 (59%). Study limitations include nonuniform outcome definitions and lack of patient-reported outcomes. Current treatment strategies based on limited reported data largely resulted in partial response. There is a paucity of high-quality studies on treatment outcomes for silicone granuloma. Future studies should compare treatment efficacies through randomized controlled trials and outcomes should be followed using long-term cohort studies.

Risk factors for granulomas in children following immunization with aluminium-adsorbed vaccines: A Danish population-based cohort study.

Aluminium-adsorbed vaccines may in some children cause severely itching nodules at the injection site, known as vaccination granulomas. To investigate vaccine-, child- and maternal-level risk factors for the development of vaccination granulomas following immunization with aluminium-adsorbed vaccines. A Danish population-based cohort study with 553 932 children born in Denmark from 1 January 2009 to 31 December 2018, vaccinated with an aluminium-adsorbed vaccine during the first year of life, followed until 31 December 2020. Poisson regression was used to estimate granuloma rate ratios according to the type of adjuvant, accumulated dose of aluminium, timing of vaccination appointments, sex, gestational age, having siblings with granulomas, maternal age and maternal ethnicity. We identified 1901 vaccination granuloma cases (absolute risk, 0.34%). Among vaccine level factors, revaccination (third vs. first vaccination appointment, adjusted rate ratio [RR] 1.26, 95% confidence interval [CI] 1.03-1.55), the specific adjuvant used (aluminium phosphate vs. hydroxide, RR 0.58, 95% CI 0.48-0.70) and dosage (≥1.0mg vs. <1.0mg, RR 1.34, 95% CI 1.19-1.52) were associated with risk of granulomas; the timing of vaccination appointments was not. Among child-level factors, female sex (vs. males, RR 1.12, 95% CI, 1.02-1.22), prematurity (vs. term birth, RR 0.71, 95% CI, 0.54-0.93) and having sibling(s) with granulomas (vs. no siblings with granulomas, RR 46.15, 95% CI, 33.67-63.26) were associated with risk of granulomas. Among maternal-level factors, non-Danish ethnicity (vs. Danish, RR 0.51, 95% CI, 0.42-0.63) and young maternal age (<20 years vs. 20-39 years, RR 0.46, 95% CI 0.25-0.83) were associated with risk of granulomas. Several risk factors for vaccination granulomas at the vaccine, child and maternal levels, were identified. Reducing the dose of aluminium or replacing aluminium hydroxide with aluminium phosphate could reduce the risk of granulomas. However, this must be balanced against the potential for reduced immunogenicity.

The cardiac sarcoidosis consortium: elucidating a mysterious disease through collaborative research

Cardiac sarcoidosis (CS) is an inflammatory disease of unknown aetiology that can lead to life-threatening arrhythmias, heart failure, and death. The hallmark pathophysiology involves the development of noncaseating granulomas in cardiac tissue disrupting normal electrical signalling and ultimately impairing cardiac pump function. Advanced cardiac imaging has improved the clinician’s ability to detect the disease, and there has been a significant rise in the number of patients diagnosed with this disorder in the last 20 years. Critical knowledge gaps remain in the domains of aetiology, genetic basis, and immunological mechanisms. There is also uncertainty as to the most appropriate diagnostic criteria, risk stratification, and treatments. The CS literature is mostly comprised of case reports and small retrospective studies; high-quality data from randomized controlled trials are lacking. After collaborating on a multicentre analysis of safety and efficacy of implantable cardioverter defibrillator (ICD) in CS,1 the founding members [Dr Thomas Crawford and Dr Frank Bogun (University of Michigan), Dr William Sauer (then at the University of Colorado), and Dr Kenneth Ellenbogen and Dr Jordana Kron (Virginia Commonwealth University)] established an international, prospective registry, the Cardiac Sarcoidosis Consortium (CSC). The consortium identified five primary aims (Figure 1). The CSC has advocated for inclusion of CS sessions at major national and international meetings and proposed and championed the development of the first CS-specific guidelines, which resulted in the 2014 Heart Rhythm Society Expert Consensus Statement on the Diagnosis and Management of Arrhythmias Associated with Cardiac Sarcoidosis.2 Since the inception of the CSC, we have witnessed an increase in academic interest in CS at national meetings and in research publications.

Trastuzumab-related sarcoidosis in patient with breast adenocarcinoma: Case report and review of the literature

Introduction: Sarcoidosis is a complex systemic granulomatous disease of unknown etiology, characterized by the formation of non-caseous granulomas. It has a biphasic age pattern, with higher incidence in young adults as well as in older people. Trastuzumab is a monoclonal antibody that inhibits the Human Epidermal Growth Factor Receptor (HER2) and there are few reports in the literature concerning sarcoidosis or sarcoidosis-like reactions induced by cancer immunotherapy. Case report: We reported a peculiar association between sarcoidosis and trastuzumab immunotherapy in a 38-year-old woman with breast cancer. Multiple well-defined lung nodules in a perilymphatic distribution were seen in association with opacities that tended to merge to form nodular images with irregular outlines, the so-called galaxy sign, in the posterior part of the upper left lobe. Conclusion: Herein, we also briefly review the role of neoplasic factors in sarcoidosis and immunopathological triggers to the development of granulomas in patients under trastuzumab therapy. Keywords: sarcoidosis; breast cancer; neoplasis; monoclonal antibody; trastuzumab

Chemokine production induced by Corynebacterium pseudotuberculosis in a murine model.

Corynebacterium pseudotuberculosis is the etiological agent of caseous lymphadenitis. The main clinical sign of this disease is the development of granulomas, especially in small ruminants; however, the pathways that are involved in the formation and maintenance of these granulomas are unknown. Cytokines and chemokines are responsible for the migration of immune cells to specific sites and tissues; therefore, it is possible that chemokines participate in abscess formation. This study aimed to evaluate the induction of chemokine production by two C. pseudotuberculosis strains in a murine model. A highly pathogenic (VD57) and an attenuated (T1) strain of C. pseudotuberculosis, as well as somatic and secreted antigens derived from these strains, was used to stimulate murine splenocytes. Then, the concentrations of the chemokines CCL-2, CCL-3, CCL-4, and CCL-5 and the cytokines IL-1 and TNF were measured in the culture supernatants. The VD57 strain had a higher ability to stimulate the production of chemokines when compared to T1 strain, especially in the early stages of stimulation, which can have an impact on granuloma formation. The T1 lysate antigen was able to stimulate most of the chemokines studied herein when compared to the other antigenic fractions of both strains. These results indicate that C. pseudotuberculosis is a chemokine production inducer, and the bacterial strains differ in their induction pattern, a situation that can be related to the specific behavior of each strain.

Can infections trigger sarcoidosis?

Can infections trigger sarcoidosis?

Exogenous Vitamin D3 Modulates Response of Bovine Macrophages to Mycobacterium avium subsp. paratuberculosis Infection and Is Dependent Upon Stage of Johne's Disease.

Mycobacterium avium subspecies paratuberculosis (MAP), the causative agent of ruminant enteritis, targets intestinal macrophages. During infection, macrophages contribute to mucosal inflammation and development of granulomas in the small intestine which worsens as disease progression occurs. Vitamin D3 is an immunomodulatory steroid hormone with beneficial roles in host-pathogen interactions. Few studies have investigated immunologic roles of 25-hydroxyvitamin D3 (25(OH)D3) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in cattle, particularly cattle infected with MAP. This study examined the effects of exogenous vitamin D3 on immune responses of monocyte derived macrophages (MDMs) isolated from dairy cattle naturally infected with MAP. MDMs were pre-treated with ± 100 ng/ml 25(OH)D3 or ± 4 ng/ml 1,25(OH)2D3, then incubated 24 hrs with live MAP in the presence of their respective pre-treatment concentrations. Following treatment with either vitamin D3 analog, phagocytosis of MAP by MDMs was significantly greater in clinically infected animals, with a greater amount of live and dead bacteria. Clinical cows had significantly less CD40 surface expression on MDMs compared to subclinical cows and noninfected controls. 1,25(OH)2D3 also significantly increased nitrite production in MAP infected cows. 1,25(OH)2D3 treatment played a key role in upregulating secretion of pro-inflammatory cytokines IL-1β and IL-12 while downregulating IL-10, IL-6, and IFN-γ. 1,25(OH)2D3 also negatively regulated transcripts of CYP24A1, CYP27B1, DEFB7, NOS2, and IL10. Results from this study demonstrate that vitamin D3 compounds, but mainly 1,25(OH)2D3, modulate both pro- and anti-inflammatory immune responses in dairy cattle infected with MAP, impacting the bacterial viability within the macrophage.

The Bovine Tuberculoid Granuloma.

The bovine tuberculoid granuloma is the hallmark lesion of bovine tuberculosis (bTB) due to Mycobacterium bovis infection. The pathogenesis of bTB, and thereby the process of bovine tuberculoid granuloma development, involves the recruitment, activation, and maintenance of cells under the influence of antigen, cytokines and chemokines in affected lungs and regional lymph nodes. The granuloma is key to successful control of bTB by preventing pathogen dissemination through containment by cellular and fibrotic layers. Paradoxically, however, it may also provide a niche for bacterial replication. The morphologic and cellular characteristics of granulomas have been used to gauge disease severity in bTB pathogenesis and vaccine efficacy studies. As such, it is critical to understand the complex mechanisms behind granuloma initiation, development, and maintenance.