Phagocytes are important components of the innate immune system for the body defence against infections by<unk> and other intracellular pathogens. The professional phagocytes include neutrophils, dendritic cells, macrophages and monocytes. These cells engulf the pathogens by phagocytosis and activate the adaptive immune system to facilitate the elimination of the infection. Cytokine signalling is the key for the interplay between the innate and adaptive limbs of the immune system, the most important of which is the IL12-dependent, IFNγ-mediated pathway. The phagocytes recognize<unk> and other pathogens by their pattern recognition receptors (PRR), which include Toll-like receptors (TLR) and NOD2. Once the pathogen is phagocytosed, the macrophages secrete IL12, which is a heterodimer formed by IL12p40 and IL12p35. IL12 receptors, composed of IL12Rβ1 and IL12Rβ2 subunits, are expressed on T lymphocytes and NK cells. It is associated with the signalling cascade formed by TYK and JAK2 kinases, eventually leading to STAT4 phosphorylation and nuclear translocation. The final response to IL12 stimulation is IFNγ production and secretion. The IFNγ receptor is expressed on the macrophages and other cells and consists of IFNγR1 and IFNγR2 subunits. It is associated with the signalling pathway of JAK1 and JAK2, leading to the homodimerization of STAT1 molecule. It is the common pathway for enhancing expression of a variety of IFNγ-inducible genes, accounting for the confinement and killing of intracellular pathogens. Genetic defects impairing the IL12/IFNγ pathway increase the<unk>  to<unk>  infections by impeding either the production or the response to IFNγ. Since the discovery of MSMD in 1996, multiple autosomal and two X-linked genes are identified in MSMD phenotypes, classified under the category of defects in intrinsic and innate immunity in the 2017 IUIS Phenotypic Classification for Primary Immunodeficiencies. IFNγR1 deficiency was the first identified genetic disorder described as MSMD. Mutation in genes encoding IFNγR1 can be dominant or recessive and it can lead to partial or complete deficiency of this receptor. IFNγR1 gene is located in to chromosome 6q23.3 and it is formed of 22 868 base pairs which are composed in 7 exons.
Mendelian susceptibility to mycobacterial disease
Undifferentiated connective tissue disease
Congenital fiber type disproportion
Finnish heritage disease
Skin manifestations of sarcoidosis
Environmental disease
Staphylococcal infection
Mycobacterium avium-intracellulare infection