- Exclusive Bee Venom Allergy: Risk Factors and Outcome of Immunotherapy. [Journal Article]
- IAInt Arch Allergy Immunol 2019 Jun 19; :1-7
- CONCLUSIONS: Despite the considerably high rate of VIT-ISR in patients with exclusive BV allergy, VIT can be performed safely and efficiently. C-kit mutation, and not basal serum tryptase level, seems to be a preferable biomarker for VIT-ISR in these patients.
- A case report and review of lymphocutaneous nocardiosis caused by Nocardia brasiliensis reported in China. [Journal Article]
- DTDermatol Ther 2019 Jun 19; :e13001
- Primary cutaneous nocardiosis caused by Nocardia brasiliensis is an uncommon disease. We report a Chinese woman presented with lymphocutaneous nocardiosis caused by Nocardia brasiliensis. The lesion …
Primary cutaneous nocardiosis caused by Nocardia brasiliensis is an uncommon disease. We report a Chinese woman presented with lymphocutaneous nocardiosis caused by Nocardia brasiliensis. The lesion begin with her right hand after an unknown insect sting and evolved rapidly and formed painful erythema and two subcutaneous nodules and abscesses on her right forearm in 5 days. Nocardia brasiliensis was isolated from pustule and identified by gene sequencing. The patient received two weeks of combination therapy contained infusion of Amoxilin potassioum clavinet and oral TMP/SMX and followed by a single therapy of oral TMP/SMX for 1 month and got a marked improvement. We reviewed a case of lymphocutaneous nocardiosis caused by Nocardia brasiliensis reported in China This article is protected by copyright. All rights reserved.
- cGAS-independent STING activation in response to DNA damage. [Journal Article]
- MCMol Cell Oncol 2019; 6(4):1558682
- Self-DNA has previously been thought to be protected from immune detection by compartmentalisation in the nucleus or mitochondria. Here, we describe the discovery of a signalling cascade that links t…
Self-DNA has previously been thought to be protected from immune detection by compartmentalisation in the nucleus or mitochondria. Here, we describe the discovery of a signalling cascade that links the detection of DNA damage in the nucleus to the activation of the innate immune adaptor STING (STimulator of INterfern Genes).
- Risk factors and indicators of severe systemic insect sting reactions. [Review]
- AAllergy 2019 Jun 13
- Hymenoptera venom allergy ranks among the top three causes of anaphylaxis worldwide, and approximately one quarter of sting-induced reactions are classified as severe. Fatal sting reactions are excee…
Hymenoptera venom allergy ranks among the top three causes of anaphylaxis worldwide, and approximately one quarter of sting-induced reactions are classified as severe. Fatal sting reactions are exceedingly rare, but certain factors may entail a considerably higher risk. Delayed administration of epinephrine and upright posture are situational risk factors which may determine an unfavorable outcome of the acute anaphylactic episode and should be addressed during individual patient education. Systemic mastocytosis and senior age are major, unmodifiable long-term risk factors and thus reinforce the indication for venom immunotherapy. Vespid venom allergy and male sex likewise augment the risk of severe or even fatal reactions. Further studies are required to assess the impact of specific cardiovascular comorbidities. Available data regarding potential effects of beta-blockers and/or ACE inhibitors in coexisting venom allergy are inconclusive and do not justify recommendations to discontinue guideline-directed antihypertensive treatment. The absence of urticaria/angioedema during sting-induced anaphylaxis is indicative of a severe reaction, serum tryptase elevation, and mast cell clonality. Determination of basal serum tryptase levels is an established diagnostic tool for risk assessment in Hymenoptera venom allergic patients. Measurement of platelet activating factor acetylhydrolase activity represents a complementary approach but is not available for routine diagnostic use. This article is protected by copyright. All rights reserved.
- Association between Lactic Acid Sting Test Scores, Self-Assessed Sensitive Skin Score sand Biophysical Properties in Chinses Females. [Journal Article]
- IJInt J Cosmet Sci 2019 Jun 13
- CONCLUSIONS: LAST scores correlated positively with TEWL rates. LAST scores could be used to identify subjects with sensitive skin characterized mainly by stinging and itching, but not those mainly by burning and erythema. This article is protected by copyright. All rights reserved.
- Vital Signs: Trends in Human Rabies Deaths and Exposures - United States, 1938-2018. [Journal Article]
- MMMMWR Morb Mortal Wkly Rep 2019 Jun 14; 68(23):524-528
- CONCLUSIONS: In the United States, wildlife rabies, especially in bats, continues to pose a risk to humans. Travelers also might be exposed to canine rabies in countries where the disease is still present; increased awareness of rabies while traveling abroad is needed. Vaccinating pets, avoiding contact with wildlife, and seeking medical care if one is bitten or scratched by an animal are the most effective ways to prevent rabies. Understanding the need for timely administration of PEP to prevent death is critical.
- [Radiotherapy and PD-L1 Expression]. [Journal Article]
- GTGan To Kagaku Ryoho 2019; 46(5):845-849
- The combination treatment of radiotherapy with anti-PD-1/PD-L1 antibody has been shown to significantly improve the clinical outcome of various cancers. Recent studies showthat radiotherapy has multi…
The combination treatment of radiotherapy with anti-PD-1/PD-L1 antibody has been shown to significantly improve the clinical outcome of various cancers. Recent studies showthat radiotherapy has multiple functions in modifying the tumor microenvironment, by inducing both immunostimulation and immunosuppression. The upregulation of PD-L1 expression in cancer cells interferes with the effector functions of interacting T cells. Preclinical studies demonstrate that radiotherapy induces PD-L1 upregulation by 4 pathways; (1)IFN-γ signaling,(2)EGFR pathway,(3)DNA damage signaling pathway, and(4)cGAS-STING pathway. All of these mechanisms are involved in the upregulation of PD-L1 expression in cancer cells via JAK/STAT pathway. Because the PD-1/PD-L1 interaction has been shown to be one of the major mechanisms of cancer immune escape, which leads to treatment failure, anti-PD-1/PD-L1 antibody may improve the efficacy of radiotherapy by enhancement of anti-tumor activity. In addition, PD-L1 expression is one of the biomarkers of good response to anti-PD-1/ PD-L1 antibody. Therefore, the comprehensive understanding of the mechanism underlying PD-L1 expression in response to radiotherapy is important for the establishment of optimal combination strategy. This approach could help to provide the basis for the combined therapies and promote personalized immuno-radiotherapy, although the signaling of PD-L1 upregulation induced by radiotherapy in tumors could be intricately regulated. In this article, we review previous researches which revealed the mechanisms of PD-L1 upregulation induced by radiotherapy.
- Accumulation of cytoplasmic DNA due to ATM deficiency activates the microglial viral response system with neurotoxic consequences. [Journal Article]
- JNJ Neurosci 2019 Jun 12
- ATM (ataxia-telangiectasia mutated) is a PI3K-like kinase best known for its role in the DNA damage response (DDR), especially after double strand breaks. Mutations in the ATM gene result in a condit…
ATM (ataxia-telangiectasia mutated) is a PI3K-like kinase best known for its role in the DNA damage response (DDR), especially after double strand breaks. Mutations in the ATM gene result in a condition known as ataxia-telangiectasia (A-T) that is characterized by cancer predisposition, radiosensitivity, neurodegeneration, sterility and acquired immune deficiency. We show here that the innate immune system is not spared in A-T. ATM-deficient microglia adopt an active phenotype that includes the overproduction of pro-inflammatory cytokines that are toxic to cultured neurons and likely contribute to A-T neurodegeneration. Causatively, ATM dysfunction results in the accumulation of DNA in the cytoplasm of microglia as well as a variety of other cell types. In microglia, cytoplasmic DNA primes an antiviral response via the DNA sensor, STING (stimulator of interferon genes). The importance of this response pathway is supported by our finding that inhibition of STING blocks the overproduction of neurotoxic cytokines. Cytosolic DNA also activates the AIM2 (absent in melanoma 2) containing inflammasome and induces proteolytic processing of cytokine precursors such as pro-IL-1β (Interleukin 1β). Our study enlarges the understanding of neurodegeneration in A-T and highlights the role of cytosolic DNA in the innate immune response.SIGNIFICANCE STATEMENTConventionally, the immune deficiencies found in A-T patients are viewed as defects of the B- and T-cells of the acquired immune system. In this study, we demonstrate the microglia of the innate immune system are also affected and uncover the mechanism by which this occurs. Loss of ATM activity leads to a slowing of DNA repair and an accumulation of cytoplasmic fragments of genomic DNA. This ectopic DNA induces the anti-virus response, which triggers the production of neurotoxic cytokines. This expands our understanding of the neurodegeneration found in A-T and offers potentially new therapeutic options.
- The innate immune sensor Toll-like receptor 2 controls the senescence-associated secretory phenotype. [Journal Article]
- SASci Adv 2019; 5(6):eaaw0254
- Cellular senescence is a stress response program characterized by a robust cell cycle arrest and the induction of a proinflammatory senescence-associated secretory phenotype (SASP) that is triggered …
Cellular senescence is a stress response program characterized by a robust cell cycle arrest and the induction of a proinflammatory senescence-associated secretory phenotype (SASP) that is triggered through an unknown mechanism. Here, we show that, during oncogene-induced senescence (OIS), the Toll-like receptor 2 (TLR2) and its partner TLR10 are key mediators of senescence in vitro and in murine models. TLR2 promotes cell cycle arrest by regulating the tumor suppressors p53-p21CIP1, p16INK4a, and p15INK4b and regulates the SASP through the induction of the acute-phase serum amyloids A1 and A2 (A-SAAs) that, in turn, function as the damage-associated molecular patterns (DAMPs) signaling through TLR2 in OIS. Last, we found evidence that the cGAS-STING cytosolic DNA sensing pathway primes TLR2 and A-SAAs expression in OIS. In summary, we report that innate immune sensing of senescence-associated DAMPs by TLR2 controls the SASP and reinforces the cell cycle arrest program in OIS.
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- Type I interferon induced by TLR2-TLR4-MyD88-TRIF-IRF3 controls Mycobacterium abscessus subsp. abscessus persistence in murine macrophages via nitric oxide. [Journal Article]
- IJInt J Med Microbiol 2019 Jun 01
- Mycobacterium abscessus (MAB) is an emerging, rapidly growing non-tuberculous Mycobacterium causing therapy-resistant pulmonary disease especially in patients with cystic fibrosis (CF). Smooth and ro…
Mycobacterium abscessus (MAB) is an emerging, rapidly growing non-tuberculous Mycobacterium causing therapy-resistant pulmonary disease especially in patients with cystic fibrosis (CF). Smooth and rough colony type MAB can be isolated from infected patients whereby rough colony type MAB are more often associated with severe disease. Disease severity is also associated with an alternated type I interferon (IFN-I) response of the MAB-infected patients. However the relevance of this response for the outcome of MAB infection is still unknown. In this study, we analyzed the IFNβ expression of murine macrophages infected with a MAB rough colony strain (MAB-R) isolated from a patient with progressive CF and compared it to macrophages infected with the MAB smooth colony type reference strain (MAB-S). We found that MAB-R infected macrophages expressed significantly more IFNβ mRNA and protein than MAB-S infected macrophages. Higher IFNβ induction by MAB-R was associated with higher TNF expression and intracellular killing while low IFNβ induction was associated with lower TNF expression and persistence of MAB-S. IFNβ induction was independent of the intracellular cGAS-STING recognition pathway. MAB appeared to be recognized extracellularly and induced IFNβ expression via TLR2-TLR4-MyD88-TRIF-IRF3 dependent pathways. By using macrophages lacking the IFN-I receptor we demonstrate that MAB induced IFN-I response essentially contributed to restricting MAB-R and MAB-S infections by activating macrophage Nos2 expression and nitric oxide production. Thus IFN-I seem to influence the intrinsic ability of macrophages to control MAB infections. As MAB persists over long time periods in susceptible patients, our findings suggest that virulence of MAB strains is promoted by an insufficient IFN-I response of the host.