MDA5 signaling induces type 1 IFN- and IL-1-dependent lung vascular permeability which protects mice from opportunistic fungal infection

Davis, Michael J.; Martin, Rachel E.; Pinheiro, Giovana M.; Hoke, Elizabeth S.; Moyer, Shannon; Mayer‐Barber, Katrin D.; Chang, Yun C.; Kwon‐Chung, Kyung J.

doi:10.3389/fimmu.2022.931194

Cited by 3 publications

(4 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A study by Oliveira et al [48] suggested that IAV infection induces the secretion of type 1 interferons (IFN-a and IFN-b), which are considered key cytokines in the host defence against the fungus Cryptococcus gattii. Moreover, Flesch et al [49] and Davis et al [50] reported that IFN-c promoted macrophage phagocytosis and killing of fungi. C. gattii is an emerging and still poorly understood pathogen, and inflammatory responses resulting in reduced IFNc may be responsible for increased susceptibility to secondary C. gattii infection.…”

Section: Superinfection Of Fungi and Virusesmentioning

confidence: 99%

“…As occurs during IAV infection, during infection with influenza B virus, the bronchial ciliated epithelium is stripped and local haemorrhage and necrosis may occur, which can cause dual infection with bacteria or fungi. Additionally, the loss of ciliary function of the bronchial tree during acute influenza B virus infection may predispose patients to invasive fungal infections [49][50][51].…”

Section: Superinfection Of Fungi and Virusesmentioning

confidence: 99%

“…In addition to the immunosuppression caused by AM depletion, the interaction of two or more pathogens during co-infections plays a role in other host immune responses, such as the regulation of immunity by IFN-a/b/c, the effect of pathogens on T-cell activity, the ability of toll-like receptor (TLR)4 to recognize pathogens, and innate immune activation [49,50]. As described above, binding of MMTV to bacterial LPS triggers TLR4 and the subsequent IL-6-dependent induction of the inhibitory cytokine IL-10, allowing MMTV to undergo immune escape and damage the immune system [14] (Fig.…”

Section: Immune Modulationmentioning

confidence: 99%

“…[49] and Davis et al. [50] reported that IFN‐γ promoted macrophage phagocytosis and killing of fungi. C. gattii is an emerging and still poorly understood pathogen, and inflammatory responses resulting in reduced IFN‐γ may be responsible for increased susceptibility to secondary C. gattii infection.…”

Section: The Commensalism Of Microbesmentioning

confidence: 99%

See 3 more Smart Citations

Interactions among microorganisms open up a new world for anti‐infectious therapy

Zhang

et al. 2022

The FEBS Journal

View full text Add to dashboard Cite

The human microbiome, containing bacteria, fungi, and viruses, is a community that coexists peacefully with humans most of the time, but with the potential to cause disease under certain conditions. When the environment changes or certain stimuli are received, microbes may interact with each other, causing or increasing the severity of disease in a host. With the appropriate methods, we can make these microbiota work for us, creating new applications for human health. This review discusses the wide range of interactions between microorganisms that result in an increase in susceptibility to, severity of, and mortality of diseases, and also briefly introduces how microorganisms interact with each other directly or indirectly. The study of microbial interactions and their mechanisms has revealed a new world of treatments for infectious disease. The regulation of the balance between intestinal flora, the correct application of probiotics, and the development of effective drugs by symbiosis all demonstrate the great contributions of the microbiota to human health and its powerful potential value. Consequently, the study of interactions between microorganisms plays an essential role in identifying the causes of diseases and the development of treatments.

show abstract

Section: Superinfection Of Fungi and Virusesmentioning

confidence: 99%

Section: Superinfection Of Fungi and Virusesmentioning

confidence: 99%

Section: Immune Modulationmentioning

confidence: 99%

Section: The Commensalism Of Microbesmentioning

confidence: 99%

See 2 more Smart Citations

Interactions among microorganisms open up a new world for anti‐infectious therapy

Zhang

et al. 2022

The FEBS Journal

View full text Add to dashboard Cite

show abstract

GMPR2-MDA5 interaction bridged the cell junction and anti-GCRV immune

Sun,

Li,

Tang

et al. 2024

Aquaculture

View full text Add to dashboard Cite

Inbred SJL mice recapitulate human resistance to Cryptococcus infection due to differential immune activation

Davis,

Martin,

Pinheiro

et al. 2023

mBio

View full text Add to dashboard Cite

Cryptococcosis remains a significant threat to human health. While the popular C57BL/6J mouse model of cryptococcosis has some advantages, there are some serious shortcomings that limit the ability of researchers to address the disease. Since humans are resistant to environmental cryptococcal infection until rendered immunodeficient while C57BL/6J mice are innately susceptible, we screened 15 inbred mouse strains for resistance to Cryptococcus infection. The SJL/J mouse strain was unusually resistant to several virulent strains of Cryptococcus while the closely related FVB/J strain was susceptible. The infection pathobiology in SJL/J mice and susceptible mice was similar for the first 7–10 days then markedly diverged toward pathogen clearance. Interferon-gamma (IFN-γ) expression was critical for SJL/J resistance while tumor necrosis factor-alpha was also important. Both CD4 and CD8 T cells produced IFN-γ and were collectively critical. While IL-17 and associated cytokines were expressed in SJL/J mice, IL-17 inhibition did not affect the outcome of infection. Unlike the C57BL/6J, infected SJL/J mice failed to express Th2/atopy-type cytokines even when rendered susceptible by IFN-γ blockade or infection with an alternative fatal cryptococcal strain virulent in SJL/J. These data suggest that the atopic-type response typically associated with the C57BL/6J model is not critical for susceptibility. The productive immune response in SJL/J mice resulted in immune memory that protected mice from reinfection. The SJL/J cryptococcal resistance phenotype was associated with a strong genetic linkage from regions located in chromosomes 2 and 11 suggesting strain-specific modifiers contribute to disease severity. Thus, SJL/J mice are an exciting alternative animal model for cryptococcal pathobiology. IMPORTANCE Cryptococcosis studies often utilize the common C57BL/6J mouse model. Unfortunately, infection in these mice fails to replicate the basic course of human disease, particularly hampering immunological studies. This work demonstrates that SJL/J mice can recapitulate human infection better than other mouse strains. The immunological response to Cryptococcus infection in SJL/J mice was markedly different from C57BL/6J and much more productive in combating this infection. Characterization of infected mice demonstrated strain-specific genetic linkage and differential regulation of multiple important immune-relevant genes in response to Cryptococcus infection. While our results validate many of the previously identified immunological features of cryptococcosis, we also demonstrate limitations from previous mouse models as they may be less translatable to human disease. We concluded that SJL/J mice more faithfully recapitulate human cryptococcosis serving as an exciting new animal model for immunological and genetic studies.

show abstract

MDA5 signaling induces type 1 IFN- and IL-1-dependent lung vascular permeability which protects mice from opportunistic fungal infection

Cited by 3 publications

References 49 publications

Interactions among microorganisms open up a new world for anti‐infectious therapy

Interactions among microorganisms open up a new world for anti‐infectious therapy

GMPR2-MDA5 interaction bridged the cell junction and anti-GCRV immune

Inbred SJL mice recapitulate human resistance to Cryptococcus infection due to differential immune activation

Contact Info

Product

Resources

About