Background: The secreted enzyme EndoS, an endoglycosidase from Streptococcus pyogenes, hydrolyzes the N-linked glycan of the constant region of immunoglobulin G (IgG) heavy chain and renders the antibody unable to interact with Fc receptors and elicit effector functions. In this study we couple targeted allelic replacement mutagenesis and heterologous expression to elucidate the contribution of EndoS to group A Streptococcus (GAS) phagocyte resistance and pathogenicity in vitro and in vivo.
Results: Knocking out the EndoS gene in GAS M1T1 background revealed no significant differences in bacterial survival in immune cell killing assays or in a systemic mouse model of infection. However, exogenous addition and heterologous expression of EndoS was found to increase GAS resistance to killing by neutrophils and monocytes in vitro. Additionally, heterologous expression of EndoS in M49 GAS increased mouse virulence in vivo.
Conclusions: We conclude that in a highly virulent M1T1 background, EndoS has no significant impact on GAS phagocyte resistance and pathogenicity. However, local accumulation or high levels of expression of EndoS in certain GAS strains may contribute to virulence.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3125321 | PMC |
http://dx.doi.org/10.1186/1471-2180-11-120 | DOI Listing |
JCI Insight
January 2025
Department of Radiology, and.
Lung cancer is the leading cause of cancer deaths in the United States. New targeted therapies against the once-deemed undruggable oncogenic KRAS are changing current therapeutic paradigms. However, resistance to targeted KRAS inhibitors almost inevitably occurs; resistance can be driven by tumor cell-intrinsic changes or by changes in the microenvironment.
View Article and Find Full Text PDFJCI Insight
January 2025
Department of Immunology and.
Tumor-associated macrophages (TAMs) are one of the key immunosuppressive components in the tumor microenvironment (TME) and contribute to tumor development, progression, and resistance to cancer immunotherapy. Several reagents targeting TAMs have been tested in preclinical and clinical studies, but they have had limited success. Here, we show that a unique reagent, FF-10101, exhibited a sustained inhibitory effect against colony-stimulating factor 1 receptor by forming a covalent bond and reduced immunosuppressive TAMs in the TME, which led to strong antitumor immunity.
View Article and Find Full Text PDFFASEB Bioadv
January 2025
Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics The First Dongguan Affiliated Hospital, Guangdong Medical University Dongguan Guangdong China.
Copper is a vital trace element crucial for mediating interactions between and macrophages. Within these immune cells, copper modulates oxidative stress responses and signaling pathways, enhancing macrophage immune functions and facilitating clearance. Conversely, copper may promote escape from macrophages through various mechanisms: inhibiting macrophage activity, diminishing phagocytic and bactericidal capacities, and supporting survival and proliferation.
View Article and Find Full Text PDFFront Immunol
January 2025
Centre of Experimental Medicine and Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, India.
Understanding the development and maintenance of immunological memory is important for efforts to eliminate parasitic diseases like leishmaniasis. Leishmaniasis encompasses a range of pathologies, resulting from infection with protozoan parasites belonging to the subgenera and of the genus A striking feature of these infections is that natural or drug-mediated cure of infection generally confers life-long protection against disease. The generation of protective T cell responses are necessary to control infections.
View Article and Find Full Text PDFJ Transl Med
January 2025
Department of General Surgery of Otorhinolaryngology Head and Neck, The Sixth Affiliated Hospital, Sun Yat-Sen University, No.26, Erheng Road, Yuancun, Tianhe District, Guangzhou, 510655, China.
Purpose: Tumor-associated macrophages (TAMs) are pivotal immune cells within the tumor microenvironment (TME), exhibiting dual roles across various cancer types. Depending on the context, TAMs can either suppress tumor progression and weaken drug sensitivity or facilitate tumor growth and drive therapeutic resistance. This study explores whether targeting TAMs can suppress the progression of head and neck squamous cell carcinoma (HNSCC) and improve the efficacy of chemotherapy.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!