Host susceptibility to non-tuberculous mycobacterial infections

Abstract

Non-tuberculous mycobacteria cause a broad range of clinical disorders, from cutaneous infections, such as cervical or intrathoracic lymphadenitis in children, to disseminated infections at all ages. Recognition of the underlying immune defect is crucial for rational treatment, preventive care, family screening, and, in some cases, transplantation. So far, at least seven autosomal mutations (in IL12B, IL12RB1, ISG15, IFNGR1, IFNGR2, STAT1, and IRF8) and two X-linked mutations (in IKBKG and CYBB), mostly presenting in childhood, have been reported to confer susceptibility to disseminated non-tuberculous mycobacterial infection. GATA2 defi ciency and antiinterferon γ autoantibodies also give rise to disseminated infection, typically in late childhood or adulthood. Furthermore, isolated pulmonary non-tuberculous mycobacterial infection has been increasing in prevalence in people without recognised immune dysfunction. In this Review, we discuss how to detect and diff erentiate host susceptibility factors underlying localised and systemic non-tuberculous mycobacterial infections.

Cryptococcosis in Anti-Interferon-Gamma Autoantibody-Positive Patients: a Different Clinical Manifestation from HIV-Infected Patients

“…While IFN-g Ab positive patients have less severe disease, NTM is the most common OI in this patient group (3), and their clinical course is more protracted. The difference in immune defects, such as Mendelian susceptibility to mycobacterial disease, which consists of 9 genetic defects (IFNGR1, IFNGR2, STAT1, IL12B, IL1RB1, ISG15, IRF8, NEMO, and CYBB), have been reported to confer susceptibility to disseminated NTM but variable susceptibility to other intracellular opportunistic infections (4). Levels of IFN-g Ab might be used to predict the type and number of OIs in these patients, but this needs further investigation.…”

“…Ninety-six percent of patients with IFN-g Ab have multiple opportunistic infections (3). The presence of IFN-g Ab alters the IFN-g-interleukin (IL)-12 axis which is critical for the control of mycobacteria and other intracellular opportunistic pathogens (4).…”

Nontuberculous mycobacterial lung disease: ecology, microbiology, pathogenesis, and antibiotic resistance mechanisms

“…Host defense against mycobacteria depends on the action of cell-mediated immunity, effected by interactions between the myeloid (monocytes, macrophages, and dendritic cells) and the lymphoid cells (T cells and natural killer cells) [121].…”

“…There are at least seven autosomal mutations and two X-linked mutations that have been associated with disseminated disease, usually occurring in childhood [121]. Three of the autosomal genes are implicated in the control of IFN-γ production: IL12B, IL12RB1, and ISG15 to a wide range of disease phenotypes previously called the "monocytopenia with M. avium complex syndrome" [121].…”

Interferon-β controls non-tuberculous mycobacterial infection in mice

“…6 Thus, like TB, mutations in the IFN-g receptor or IFN-g signaling cascade, and mutations in the cytokine receptors which promote Th-1 response such as IL-12R, predispose individuals to NTM infections. 7 Recently, an association between increased eosinophil counts and IgE levelsconsidered as surrogate markers for the Th-2 type immune response -and pulmonary MAC infection has been reported. 8 Autoantibodies against IFN-g have also been reported to predispose to NTM infection.…”