Mycobacterium Intracellulare Infection Research Articles

Early IL-17A production helps establish Mycobacterium intracellulare infection in mice.

Nontuberculous mycobacteria (NTM) infection is common in patients with structural lung damage. To address how NTM infection is established and causes lung damage, we established an NTM mouse model by intranasal inoculation of clinical isolates of M. intracellulare. During the 39-week course of infection, the bacteria persistently grew in the lung and caused progressive granulomatous and fibrotic lung damage with mortality exceeding 50%. Lung neutrophils were significantly increased at 1 week postinfection, reduced at 2 weeks postinfection and increased again at 39 weeks postinfection. IL-17A was increased in the lungs at 1-2 weeks of infection and reduced at 3 weeks postinfection. Depletion of neutrophils during early (0-2 weeks) and late (32-34 weeks) infection had no effect on mortality or lung damage in chronically infected mice. However, neutralization of IL-17A during early infection significantly reduced bacterial burden, fibrotic lung damage, and mortality in chronically infected mice. Since it is known that IL-17A regulates matrix metalloproteinases (MMPs) and that MMPs contribute to the pathogenesis of pulmonary fibrosis, we determined the levels of MMPs in the lungs of M. intracellulare-infected mice. Interestingly, MMP-3 was significantly reduced by anti-IL-17A neutralizing antibody. Moreover, in vitro data showed that exogenous IL-17A exaggerated the production of MMP-3 by lung epithelial cells upon M. intracellulare infection. Collectively, our findings suggest that early IL-17A production precedes and promotes organized pulmonary M. intracellulare infection in mice, at least in part through MMP-3 production.

Simultaneous disseminated infections with intracellular pathogens: an intriguing case report of adult-onset immunodeficiency with anti-interferon-gamma autoantibodies

BackgroundSevere and disseminated non-tuberculous mycobacterial (NTM) infections are frequently linked to a genetic predisposition but acquired defects of the interferon gamma (IFNγ) / interleukin 12 (IL-12) pathway need to be considered in adult patients with persistent or recurrent infections. Neutralizing anti-IFNγ autoantibodies disrupting IFNγ signalling have been identified as the cause of a severe and unique acquired immunodeficiency syndrome with increased susceptibility to NTM and other intracellular pathogens.Case presentationAn adult Asian female with a previous history of recurrent NTM infections presented with persistent diarrhea, abdominal pain, night sweats and weight loss. Severe colitis due to a simultaneous infection with cytomegalovirus (CMV) and Salmonella typhimurium was diagnosed, with both pathogens also detectable in blood samples. Imaging studies further revealed thoracic as well as abdominal lymphadenopathy and a disseminated Mycobacterium intracellulare infection was diagnosed after a lymph node biopsy. Further diagnostics revealed the presence of high-titer neutralizing anti-IFNγ autoantibodies, allowing for the diagnosis of adult-onset immunodeficiency with anti-IFNγ autoantibodies (AIIA).ConclusionsWe here present a severe case of acquired immunodeficiency with anti-IFNγ autoantibodies with simultaneous, disseminated infections with both viral and microbial pathogens. The case illustrates how the diagnosis can cause considerable difficulties and is often delayed due to unusual presentations. Histological studies in our patient give further insight into the pathophysiological significance of impaired IFNγ signalling. B-cell-depleting therapy with rituximab offers a targeted treatment approach in AIIA.

Alpha-1-Antitrypsin Enhances Primary Human Macrophage Immunity Against Non-tuberculous Mycobacteria.

Rationale: The association between non-tuberculous mycobacterial lung disease and alpha-1-antitrypsin (AAT) deficiency is likely due, in part, to underlying emphysema or bronchiectasis. But there is increasing evidence that AAT itself enhances host immunity against microbial pathogens and thus deficiency could compromise host protection.Objectives: The goal of this project is to determine if AAT could augment macrophage activity against non-tuberculous mycobacteria.Methods: We compared the ability of monocyte-derived macrophages cultured in autologous plasma that were obtained immediately before and soon after AAT infusion—given to individuals with AAT deficiency—to control an ex vivo Mycobacterium intracellulare infection.Measurements and Main Results: We found that compared to pre-AAT infused monocyte-derived macrophages plus plasma, macrophages, and contemporaneous plasma obtained after a session of AAT infusion were significantly better able to control M. intracellulare infection; the reduced bacterial burden was linked with greater phagosome-lysosome fusion and increased autophagosome formation/maturation, the latter due to AAT inhibition of both M. intracellulare–induced nuclear factor-kappa B activation and A20 expression. While there was a modest increase in apoptosis in the M. intracellulare-infected post-AAT infused macrophages and plasma, inhibiting caspase-3 in THP-1 cells, monocyte-derived macrophages, and alveolar macrophages unexpectedly reduced the M. intracellulare burden, indicating that apoptosis impairs macrophage control of M. intracellulare and that the host protective effects of AAT occurred despite inducing apoptosis.Conclusion: AAT augments macrophage control of M. intracellulare infection through enhancing phagosome-lysosome fusion and autophagy.

Granulomatous Rhinitis in a Horse due to Mycobacterium intracellulare Infection

Mycobacterial infections in horses are uncommon, but are caused most frequently by Mycobacterium bovis of the Mycobacterium tuberculosis complex or Mycobacterium avium of the M. avium complex. Disease caused by Mycobacterium intracellulare, the second most common species within the M. avium complex, has not been reported in horses to date. Mycobacteriosis in horses most often presents as enteric, pulmonary or, rarely, systemic disease. Here we report a case of M. intracellulare infection in a horse presenting as a granulomatous nasal mass.

Atypical macrophages in disseminated Mycobacterium intracellulare infection.

Atypical macrophages in disseminated Mycobacterium intracellulare infection.

Mycobacterium intracellulare Infection Mimicking Progression of Scleroderma

This case report describes a patient with scleroderma who developed Mycobacterium intracellulare infection, which for more than a year mimicked worsening of her connective tissue disorder. The patient was diagnosed with scleroderma based on puffy fingers that developed into sclerodactyly, abnormal nail fold capillaries, interstitial lung disease, Raynaud's phenomenon, esophageal dysmotility, and positivity for rheumatoid factor and anti-SSA antibodies. She developed massive inflammatory changes of the cutis, the subcutis, and the muscle fasciae of the right leg, that after several failed attempts of immunosuppressive treatments were found to be caused by Mycobacterium intracellulare. While she was receiving high-dose prednisolone, as worsening of her connective tissue disease was suspected to be the cause of the inflammatory changes, she had Listeria monocytogenes meningitis and was hospitalized for several weeks, but she recovered from this without sequelae. After Mycobacterium intracellulare infection was diagnosed, she was treated with clarithromycin and rifampicin. Her skin manifestations, arthralgias, and fatigue improved considerably, and the wounds of the right leg healed, unfortunately with significant scarring. Immunodeficiency testing was unremarkable. In summary, an infection with Mycobacterium intracellulare was mistaken for an unusually severe progression of scleroderma.

A Human T Lymphotropic Virus Type 1 Carrier Coinfected with <i>Mycobacterium intracellulare</i> and <i>Pneumocystis jirovecii</i> with a Characteristic Compositional Change of Bone Marrow Cells

Human T lymphotropic virus type 1 (HTLV-1) is endemic in the southern part of Japan. Infection of the virus can cause adult T cell leukemia/lymphoma (ATL), while most infected individuals remain in a carrier state for a long period of time. Although rare cases of carriers, like ATL patients, who developed opportunistic infections, have been reported, hematological changes of carriers who are prone to opportunistic infections have not been well defined. Here, we present a case of an HTLV-1 carrier who developed Mycobacterium intracellulare infection and Pneumocystis jirovecii pneumonia (PcP) simultaneously. Flow cytometric analysis of bone marrow cells revealed an aberrant compositional change similar to that in ATL patients. This suggests the presence of a pre-ATL state prior to the development of ATL, which is notable in terms of underlying cellular immunodeficiency.

IL12Rβ1 Defect Presenting with Massive Intra-Abdominal Lymphadenopathy Due to Mycobacterium intracellulare Infection: A Case Report

IL12Rβ1 Defect Presenting with Massive Intra-Abdominal Lymphadenopathy Due to Mycobacterium intracellulare Infection: A Case Report

A spatial epidemiological analysis of nontuberculous mycobacterial infections in Queensland, Australia.

BackgroundThe epidemiology of infections with nontuberculous mycobacteria (NTM) has been changing and the incidence has been increasing in some settings. The main route of transmission to humans is considered to be from the environment. We aimed to describe spatial clusters of cases of NTM infections and to identify associated climatic, environmental and socio-economic variables.MethodsNTM data were obtained from the Queensland Mycobacterial Reference Laboratory for the period 2001–2011. A Bayesian spatial conditional autoregressive model was constructed at the postcode level, with covariates including soil variables, maximum, mean and minimum rainfall and temperature, income (proportion of population earning < $32,000 and < $52,000) and land use category.ResultsSignificant clusters of NTM infection were identified in the central Queensland region overlying the Surat sub-division of the Great Artesian Basin, as well as in the lower North Queensland Local Government Area known as the Whitsunday region. Our models estimated an expected increase of 21% per percentage increase of population earning < $52,000 (95% CI 9–34%) and an expected decrease of 13% for every metre increase of average topsoil depth for risk of Mycobacterium intracellulare infection (95% CI -3 – -22%). There was an estimated increase of 79% per mg/m3 increase of soil bulk density (95% CI 26–156%) and 19% decrease for every percentage increase in population earning < $32,000 for risk of M. kansasii infection (95% CI -3 – -49%).ConclusionsThere were distinct spatial clusters of M. kansasii, M. intracellulare and M. abscessus infections in Queensland, and a number of socio-ecological, economic and environmental factors were found to be associated with NTM infection risk.

MYCOBACTERIUM INTRACELLULAREINFECTION IN A CAPYBARA (HYDROCHOERUS HYDROCHAERIS)

This report describes the first case of Mycobacterium intracellulare infection with typical granulomatous lesions of mycobacteriosis in a capybara (Hydrochoerus hydrochaeris). The individual was a captive-bred young female, part of the control group of an experimental study on stress. Multiple granulomatous lesions were detected in a mesenteric lymph node of this young female. Mycobacterial infection was confirmed by bacteriologic culture and molecular identification methods. Clinical lesions were characterized by histopathology.

Disseminated Mycobacterium intracellulare infection in a broad-snouted caiman Caiman latirostris

A 10 yr old broad-snouted caiman Caiman latirostris from a small Dutch animal park was presented with long-term variable periods of anorexia and weight loss. Blood chemistry showed slightly elevated uric acid levels and low ionised calcium concentration. Ultrasonographical thickening of the intestinal wall in the region of the duodenum was evident. Pathological changes were a thickening of the wall of 90% of the small intestines, enlarged spleen with multifocal white foci and an enlarged light-brown liver. Histopathological lesions consisted of disseminated granulomas in the intestinal wall, the liver and the spleen. Multinucleated giant cells and epitheloid macrophages were abundant. Ziehl-Neelsen staining showed numerous intralesional acid-fast bacteria. Polymerase chain reaction for Mycobacterium intracellulare was positive.

A novel mutation in IFN-γ receptor 1 presenting as multisystem Mycobacterium intracellulare infection

We report the case of a 15-month-old boy with disseminated Mycobacterium intracellulare infection causing multifocal osteomyelitis and pneumonia. A novel heterozygous frameshift mutation (805delT) encoding the IFN-γ receptor 1 (IFNGR1) was identified. Cell surface receptor expression was upregulated, consistent with dominant negative effect. After antimycobacterial treatment, the infection resolved and he has remained healthy on antimycobacterial prophylaxis with the exception of a diarrheal illness.

Cutaneous Mycobacterium intracellulare Infection in an Immuno�competent Person

Mycobacterium intracellulare-caused pulmonary infections have mostly been reported in immunocompromised hosts, while cutaneous M. intracellulare infections are rare. We describe here an immunocompetent patient with cutaneous lesions due to M. intracellulare, which was diagnosed by acid-fast staining, in vitro culture, histopathology, and PCR-restriction fragment length polymorphism analysis and gene sequencing of heat-shock protein (hsp) 65 and 16S rDNA genes. In vitro susceptibility testing was also carried out and the patient was successfully treated with clarithromycin, rifampicin, and ethambutol.

Cutaneous Mycobacterium intracellulare infection presenting as multiple asymptomatic papulonodules in an immunocompetent adult: A case report and review of the literature

Abstract Disseminated cutaneous nontuberculous mycobacteria infection is rare in immunocompetent hosts. We report a case of Mycobacterium intracellulare infection in an immunocompetent patient presenting with simultaneously developing multiple asymptomatic cutaneous papulonodules. The possibility of lung lesions as the primary focus is suspected. We review the literature for other cases of multiple cutaneous M avium complex infections in immunocompetent hosts. There are differences in the virulence of M avium and M intracellulare, and hence in the underlying immune status of the hosts.

A case of Mycobacterium intracellulare infection with chronic empyema

A 83-year-old man had been treated for pulmonary infiltration was referred to a nearby hospital because of slight fever and cough. His chest radiograph and CT showed right chronic empyema, and in which pleural aspirate was smear positive for acid-fast bacilli and positive for PCR-Mycobacterium intracellulare. He was diagnosed as chronic empyema caused by M. intracellulare. A month later exacerbation of bronchopleural fistula was observed and M. intracellulare infection expanded into the lung. He was treated with combined use of ethambutol, rifampicin, clarithromycin, and streptomycin for six months, and his chest radiograph showed improvement, however, finally he died as he was in advanced age and emaciation due to chronic lung infection.

Control of Mycobacterium fortuitum and Mycobacterium intracellulare infections with respect to distinct granuloma formations in livers of BALB/c mice

Mycobacterium fortuitum is a rapidly growing nontuberculous Mycobacterium that can cause a range of diseases in humans. Complications from M. fortuitum infection have been associated with numerous surgical procedures. A protective immune response against pathogenic mycobacterial infections is dependent on the granuloma formation. Within the granuloma, the macrophage effector response can inhibit bacterial replication and mediate the intracellular killing of bacteria. The granulomatous responses of BALB/c mice to rapidly and slowly growing mycobacteria were assessed in vivo and the bacterial loads in spleens and livers from M. fortuitum and Mycobacterium intracellulare-infected mice, as well as the number and size of granulomas in liver sections, were quantified. Bacterial loads were found to be approximately two times lower in M. fortuitum-infected mice than in M. intracellulare-infected mice and M. fortuitum-infected mice presented fewer granulomas compared to M. intracellulare-infected mice. These granulomas were characterized by the presence of Mac-1+ and CD4+ cells. Additionally, IFN-γmRNA expression was higher in the livers of M. fortuitum-infected mice than in those of M. intracellulare-infected mice. These data clearly show that mice are more capable of controlling an infection with M. fortuitum than M. intracellulare. This capacity is likely related to distinct granuloma formations in mice infected with M. fortuitum but not with M. intracellulare.

Non-tuberculous Mycobacterial Lung Disease Presenting as a Solitary Pulmonary Nodule

We report a case of Mycobacterium intracellulare pulmonary infection presenting as a solitary pulmonary nodule (SPN). A 35-year-old male was admitted due to a SPN in the right upper lobe which was detected on the chest radiography being examed due to recurrent cough for 1 year. The computed tomography (CT) revealed a spiculated nodule containing air-bronchogram, which was suspicious of malignancy. We performed transbronchial biopsy and the pathology showed granulomatous inflammation with caseous necrosis. Under the presumptive diagnosis of pulmonary tuberculosis, we started anti-tuberculous medication including isoniazid, rifampin, ethambutol, and pyrazinamide. In one month, however, the sputum culture was positive for Mycobacterium intracellulare. The follow-up chest CT showed slight aggravation of the previous lesions. Under the final diagnosis of Mycobacterium intracellulare pulmonary infection presenting as a solitary pulmonary nodule, we changed the regimen to rifampin, ethambutol, and clarithromycin. The follow-up chest CT after the completion of treatment, revealed resolution of the previous lesions.

Mycobacterium intracellulare pulmonary infection in an immunosuppressed child with Crohnʼs Disease

Mycobacterium intracellulare pulmonary infection in an immunosuppressed child with Crohnʼs Disease

A Case of Disseminated Mycobacterium intracellulare Infection in an Immunocompromised Host

We report a case of disseminated Mycobacterium intracellulare infection in a 31-year-old man who had been diagnosed as having dermatomyositis and systemic lupus erythematosus 3-years prior. The patient developed a left pleural effusion M. intracellulare was repeatedly isolated from the pleural fluid. After antimycobacterial treatment, the patient’s pleural effusion resolved, but a left knee joint effusion developed newly and M. intracellulare was cultured from the joint fluid. At present, the patient has been taking antimycobacterial medication for 15 months but his left knee joint fluid remains positive for M. intracellulare. To our knowledge, this is the second reported case of disseminated NTM infection in a non-HIV infected patient in Korea.

Mycobacterium intracellulare Pulmonary Infection which Co-existed and Mimicked Lung Cancer

We report a case of Mycobacterium intracellulare (M. intracellulare) pulmonary infection with co-existing lung cancer and presenting as a solitary pulmonary nodule requiring differentiation from lung cancer. Computed tomography showed two nodules (20 mm) with spicula formation and pleural indentation on the right lower lobe of the lung (right S6 and S8). Transbronchial biopsies from the right S6 and S8 nodules revealed mycobacteriosis and adenocarcinoma, respectively. Thereafter, a right lower lobectomy was performed. Cases of pulmonary M. intracellulare disease with solitary nodule are rare. Moreover, M. intracellulare pulmonary infection with co-existing lung cancer is extremely rare.