scholarly journals Co-infection of macrophages modulates interferon gamma and tumor necrosis factor-induced activation against intracellular pathogens.

1990 ◽  
Vol 172 (3) ◽  
pp. 977-980 ◽  
Author(s):  
C M Black ◽  
L E Bermudez ◽  
L S Young ◽  
J S Remington
Keyword(s):  
Interferon Gamma ◽  
Mononuclear Phagocytes ◽  
Intracellular Pathogens ◽  
Inhibition Of Growth ◽  
Static Activity ◽  
Acquired Immunodeficiency ◽  
Mycobacterium Avium Intracellulare ◽  
Cytokine Stimulation ◽  
Immunodeficiency Syndrome ◽  
Necrosis Factor

Co-infection of macrophages (M phi) with Toxoplasma gondii and Mycobacterium avium-intracellulare complex (MAC) has been observed in patients with acquired immunodeficiency syndrome (AIDS). In this study we have demonstrated that co-infected murine M phi respond differently to cytokine stimulation than M phi infected with either of the microorganisms alone. Whereas treatment with interferon gamma (IFN-gamma) activated both single and co-infected groups of M phi to kill T. gondii, treatment with TNF did not influence the rate of MAC growth in co-infected M phi, in contrast with the inhibition of growth observed in MAC-infected M phi. These results suggest that in AIDS patients suffering infection with multiple intracellular pathogens, the ability of cytokines to stimulate microbicidal or static activity in mononuclear phagocytes can be impaired by the presence of more than one of the intracellular organisms.

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

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Malte Roerden ◽  
Rainer Döffinger ◽  
Gabriela Barcenas-Morales ◽  
Stephan Forchhammer ◽  
Stefanie Döbele ◽  
...  
Keyword(s):  
Interferon Gamma ◽  
High Titer ◽  
Previous History ◽  
Severe Case ◽  
Lymph Node Biopsy ◽  
Microbial Pathogens ◽  
Interleukin 12 ◽  
Intracellular Pathogens ◽  
Adult Onset ◽  
Acquired Immunodeficiency

Abstract Background Severe 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 presentation An 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). Conclusions We 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.

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