Genetic susceptibility to mycobacteria and other infectious pathogens in humans

Bellamy, Richard; Hill, Adrian V. S.

doi:10.1016/s0952-7915(98)80125-8

Cited by 83 publications

(53 citation statements)

References 40 publications

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“…The lack of information available about the role of genetics and susceptibility to tuberculosis in birds contrasts to what is known in humans and other mammals (Bellamy & Hill, 1998). Both environmental and genetic factors and their interaction influence susceptibility to tuberculosis in humans (Casanova & Abel, 2002;Schurr, 2007), in laboratory animals such as rabbits and mice, and in domestic mammals (Barthel et al, 2000;Phillips et al, 2002;Di Pietrantonio & Schurr, 2005;Dannemberg, 2006).…”

Section: Discussionmentioning

confidence: 99%

Mycobacteriosis in naturally infected ring-neck doves (Streptopelia risoria): investigation of the association between feather colour and susceptibility to infection, disease and lesions type

Saggese

Tizard²,

Phalen

2008

Avian Pathology

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Section: Discussionmentioning

confidence: 99%

Mycobacteriosis in naturally infected ring-neck doves (Streptopelia risoria): investigation of the association between feather colour and susceptibility to infection, disease and lesions type

Saggese

Tizard²,

Phalen

2008

Avian Pathology

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“…The contribution of genetic polymorphisms to human variation in tuberculosis resistance has been amply demonstrated in twin, association, and linkage studies (8). As a result of this ongoing work, several genes (NRAMP1 (SLC11A1), vitamin D receptor, and HLA-DQ) have been shown to contribute to variation in tuberculosis susceptibility in human populations.…”

mentioning

confidence: 99%

The Host Resistance Locussst1Controls Innate Immunity toListeria monocytogenesInfection in Immunodeficient Mice

Boyartchuk

Rojas

Yan

et al. 2004

The Journal of Immunology

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Epidemiological, clinical, and experimental approaches have convincingly demonstrated that host resistance to infection with intracellular pathogens is significantly influenced by genetic polymorphisms. Using a mouse model of infection with virulent Mycobacterium tuberculosis (MTB), we have previously identified the sst1 locus as a genetic determinant of host resistance to tuberculosis. In this study we demonstrate that susceptibility to another intracellular pathogen, Listeria monocytogenes, is also influenced by the sst1 locus. The contribution of sst1 to anti-listerial immunity is much greater in immunodeficient scid mice, indicating that this locus controls innate immunity and becomes particularly important when adaptive immunity is significantly depressed. Similar to our previous observations using infection with MTB, the resistant allele of sst1 prevents formation of necrotic infectious lesions in vivo. We have shown that macrophages obtained from sst1-resistant congenic mice possess superior ability to kill L. monocytogenes in vitro. The bactericidal effect of sst1 is dependent on IFN-γ activation and reactive oxygen radical production by activated macrophages after infection, but is independent of NO production. It is possible that there is a single gene that controls common IFN-dependent macrophage function, which is important in the pathogenesis of infections caused by both MTB and L. monocytogenes. However, host resistance to the two pathogens may be controlled by two different polymorphic genes encoded within the sst1 locus. The polymorphic gene(s) encoded within the sst1 locus that controls macrophage interactions with the two intracellular pathogens remains to be elucidated.

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“…IFN-γ activates different effector mechanisms of phagocytic cells, which ensure appropriate control and elimination of phagocytized microorganisms. The immune response against intracellular microorganisms also involves lysis of infected cells by cytotoxic T and NK cells (2,5,6,20).…”

Section: Discussionmentioning

confidence: 99%

“…Mutations in five different genes produce this disorder: IFN-GR1, IFN-GR2, STAT1, IL12B, and IL12RB1. The main clinical characteristic of these patients is their higher susceptibility to the development of disseminated mycobacterial disease or local recurrent infections by non-tuberculosis mycobacteria and, in some cases, chronic infections by other agents such as Salmonella species and certain viruses (20,(22)(23)(24)(25)(26)(27)(29)(30)(31)(32)(33)(34)(35)(36). Many of these characteristics are similar to the clinical features observed in our patients (Table 3); therefore, a defect in one of the molecules involved in the IL-12/IFN-γ/IFN-γR/STAT-1 activation pathway is a possible explanation for their phenotype.…”

Section: Discussionmentioning

confidence: 99%

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Normal expression of IFN-gammaR in four patients with uncommon mycobacterial infection phenotypes

Rugeles

Rincón

Rugeles

et al. 2004

Braz J Med Biol Res

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Several primary immunodeficiency diseases affecting the interleukin 12/interferon gamma (IFN-γ) pathway have been identified, most of them characterized by recurrent and protracted infections produced by intracellular microorganisms, particularly by several species of mycobacteria. In the present study we analyzed the expression of IFN-γ receptor (IFN-γR) and signal transducer and activator of transcription 1 (STAT-1) in 4 children with Mycobacterium tuberculosis infection of uncommon clinical presentation. These molecules were evaluated by flow cytometry and Western blotting in B cells transformed with Epstein-Barr virus and mutations were scanned by single-strand conformational polymorphisms and DNA sequencing. The expression of IFN-γR1 was normal in all 4 patients. The genetic analysis of IFN-γR1 and IFN-γR2 coding sequences did not reveal any mutation. The expression of the STAT-1 molecule was similar in patients and healthy controls; however, when the phosphorylation of this transcription factor in response to IFN-γ activation was evaluated by Western blot, a significant lower signal was evident in one patient. These data indicate that there are no alterations in the expression or function of the IFN-γR chains in these patients. However, the low level of STAT-1 phosphorylation found in one of these patients might be explained by a defect in one of the molecules involved in the signal transduction pathway after IFN-γ interacts with its receptor. In the other three patients the inability to eliminate the mycobacteria may be due to a defect in another effector mechanism of the mononuclear phagocytes.

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Genetic susceptibility to mycobacteria and other infectious pathogens in humans

Cited by 83 publications

References 40 publications

Mycobacteriosis in naturally infected ring-neck doves (Streptopelia risoria): investigation of the association between feather colour and susceptibility to infection, disease and lesions type

Mycobacteriosis in naturally infected ring-neck doves (Streptopelia risoria): investigation of the association between feather colour and susceptibility to infection, disease and lesions type

The Host Resistance Locussst1Controls Innate Immunity toListeria monocytogenesInfection in Immunodeficient Mice

Normal expression of IFN-gammaR in four patients with uncommon mycobacterial infection phenotypes

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