Viral infections in interferon-γ receptor deficiency

Dorman, Susan E.; Uzel, Gülbû; Roesler, Joachim; Bradley, John S.; Bastian, John F.; Billman, Glenn F.; King, Susan; Filie, Armando C.; Schermerhorn, James; Holland, Steven M.

doi:10.1016/s0022-3476(99)70064-8

Cited by 165 publications

(101 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

Section: Discussionmentioning

confidence: 81%

“…The majority of patients described to date have no problems coping with any other pathogens, although some severe herpes virus infections have been described (22). The same holds true for all but one patient with partial IFN-␥R1 deficiency described to date (22). Given the mouse models, it is intriguing that no problems with T. gondii infections have been reported (23) in Control monocyte-derived macrophages were stimulated for 18 h in the presence or the absence of suboptimal (1 U/ml) or optimal (1000 U/ml) amounts of IFN-␥ with or without TNF-␣ (10 ng/ml) before infection with S. typhimurium.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Divergent Role for TNF-α in IFN-γ-Induced Killing ofToxoplasma gondiiandSalmonella typhimuriumContributes to Selective Susceptibility of Patients with Partial IFN-γ Receptor 1 Deficiency

Janssen

Wengen

Verhard

et al. 2002

The Journal of Immunology

View full text Add to dashboard Cite

Patients with defects in IFN-γ- or IL-12-mediated immunity are susceptible to infections with Salmonella and non-tuberculous mycobacteria, but rarely suffer from infections with other intracellular pathogens such as Toxoplasma gondii. Here we describe macrophage and T cell function in eight individuals with partial IFN-γ receptor 1 (IFN-γR1) deficiency due to a mutation that results in elevated cell surface expression of a truncated IFN-γR1 receptor that lacks the intracellular domain. We show that various effector mechanisms dependent on IFN-γR signaling are affected to different extents. Whereas TNF-α production was normally up-regulated in response to IFN-γ, IL-12 production and CD64 up-regulation were strongly reduced, and IFN-γ-mediated killing of the intracellular pathogens Salmonella typhimurium and T. gondii was completely abrogated in patient’s macrophages. Since these patients suffer selectively from infections with non-tuberculous mycobacteria and Salmonella, but not T. gondii, despite sero-immunity in six of eight patients, which indicates previous contact with this pathogen, we next studied the role of TNF-α as a possible immune compensatory mechanism. IFN-γ-induced killing of T. gondii appeared to be partially mediated by TNF-α, and addition of TNF-α could compensate for the abrogated killing of T. gondii in the patient’s macrophages. In contrast, IFN-γ-mediated killing of S. typhimurium appeared to be independent of TNF-α. We propose that the divergent role of TNF-α in IFN-γ-induced killing of T. gondii and S. typhimurium may at least partially explain the highly selective susceptibility of patients.

show abstract

Section: Discussionmentioning

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Divergent Role for TNF-α in IFN-γ-Induced Killing ofToxoplasma gondiiandSalmonella typhimuriumContributes to Selective Susceptibility of Patients with Partial IFN-γ Receptor 1 Deficiency

Janssen

Wengen

Verhard

et al. 2002

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Other rapidly growing mycobacterial species such as M. fortuitum but also M. avium, Salmonella, and Listeria monocytogene infections have been reported. Severe diseases caused by viruses, such as CMV and HSV, have been diagnosed each in one child (5). No other opportunistic infections were observed, and common childhood infections followed a normal course.…”

Section: Histologic and Clinical Featuresmentioning

confidence: 99%

“…Unlike children with classic immunodeficiency, who suffer from other clinical diseases caused by various viruses, bacteria, fungi, and protozoa, children with severe idiopathic BCG and NTM infection generally do not have other associated symptomatic infections apart from salmonellosis, which occurs in less than half the cases. Clinical diseases caused by cytomegalovirus, herpes simplex virus, Listeria monocytogenes, and Histoplasma capsulatum have each been found in only one patient (5)(6)(7)(8)(9).…”

mentioning

confidence: 99%

Impaired Interferon Gamma-Mediated Immunity and Susceptibility to Mycobacterial Infection in Childhood

et al. 2001

View full text Add to dashboard Cite

“…Both subgroups show an autosomal recessive (AR) inheritance. Several reports concerning patients with complete IFN-γ R1 deficiency have been published before (19)(20)(21)(22)(23)(24)(25)(26)(27).…”

Section: Introductionmentioning

confidence: 99%

Two Patients with Complete Defects in Interferon Gamma Receptor-Dependent Signaling

et al. 2007

View full text Add to dashboard Cite

Unusual susceptibility to mycobacterial infections can be caused by deleterious mutations in genes that encode the interferon-γ receptor 1 chain. Such mutations hamper the activation of macrophages by a type 1 immune response and result in enhanced survival of intracellular pathogens. We here report two patients with unusual mycobacterial infections, both diagnosed with homozygous deleterious interferon-γ receptor 1 gene mutations. Patient 1 became ill after Bacillus CalmetteGuérin vaccination at the age of 9 months and died at the age of 18 months. She carried a homozygous C71Y mutation in the extracellular part of the mature interferon-γ receptor 1 protein, resulting in the lack of detectable protein expression and absence of interferon-γ dependent signaling. Patient 2 became ill at the age of 3 years, is still alive at 19 years of age, and has suffered from five successive infection episodes with atypical mycobacteria. A homozygous splice-site mutation in intron 3 was identified, resulting in the deletion of exon 3 at the mRNA level and consequently a truncated interferon-γ receptor 1 protein with absence of the transmembrane domain. Protein expression and interferon-γ dependent signaling were not detectable.

show abstract

Viral infections in interferon-γ receptor deficiency

Cited by 165 publications

References 30 publications

Divergent Role for TNF-α in IFN-γ-Induced Killing ofToxoplasma gondiiandSalmonella typhimuriumContributes to Selective Susceptibility of Patients with Partial IFN-γ Receptor 1 Deficiency

Divergent Role for TNF-α in IFN-γ-Induced Killing ofToxoplasma gondiiandSalmonella typhimuriumContributes to Selective Susceptibility of Patients with Partial IFN-γ Receptor 1 Deficiency

Impaired Interferon Gamma-Mediated Immunity and Susceptibility to Mycobacterial Infection in Childhood

Two Patients with Complete Defects in Interferon Gamma Receptor-Dependent Signaling

Contact Info

Product

Resources

About