Interference with Lipoprotein Maturation Sensitizes Methicillin-Resistant < b > < i > Staphylococcus aureus < /i > < /b > to Human Group IIA-Secreted Phospholipase A < sub > 2 < /sub > and Daptomycin
Methicillin-resistantStaphylococcus aureus (MRSA) has been classified as a high priority pathogen by the World Health Organization underlining the high demand for new therapeutics to treat infections. Human group IIA-secreted phospholipase A2 (hGIIA) is among the most potent bactericidal proteins against Gram-positive bacteria, includingS. aureus. To determine hGIIA-resistance mechanisms of MRSA, we screened the Nebraska Transposon Mutant Library using a sublethal concentration of recombinant hGIIA. We identified and confirmed the role oflspA, encoding the lipoprotein signal peptidase LspA, as a new hGIIA resistance gene i...
Source: Journal of Innate Immunity - December 6, 2022 Category: Allergy & Immunology Source Type: research
Farewell to Professors Arne Egesten and Heiko Herwald
J Innate Immun 2022;14:581 (Source: Journal of Innate Immunity)
Source: Journal of Innate Immunity - December 6, 2022 Category: Allergy & Immunology Source Type: research
Farewell to Professors Arne Egesten and Heiko Herwald
J Innate Immun 2022;14:1 (Source: Journal of Innate Immunity)
Source: Journal of Innate Immunity - December 6, 2022 Category: Allergy & Immunology Source Type: research
The Olfactomedin-4-Defined Human Neutrophil Subsets Differ in Proteomic Profile in Healthy Individuals and Patients with Septic Shock
The specific granule glycoprotein olfactomedin-4 (Olfm4) marks a subset (1 –70%) of human neutrophils and the Olfm4-high (Olfm4-H) proportion has been found to correlate with septic shock severity. The aim of this study was to decipher proteomic differences between the subsets in healthy individuals, hypothesizing that Olfm4-H neutrophils have a proteomic profile distinc t from that of Olfm4 low (Olfm4-L) neutrophils. We then extended the investigation to septic shock. A novel protocol for the preparation of fixed, antibody-stained, and sorted neutrophils for LC-MS/MS was developed. In healthy individuals, 39 proteins sh...
Source: Journal of Innate Immunity - November 30, 2022 Category: Allergy & Immunology Source Type: research
CLIPA7 Exhibits Pleiotropic Roles in the < b > < i > Anopheles gambiae < /i > < /b > Immune Response
Clip domain serine proteases and clip domain serine protease homologs (cSPHs) are key components of serine protease cascades that drive the melanization response. Despite lacking catalytic activity, cSPHs play essential roles in regulating melanization, but the spectrum of functions they catalyze within and outside these cascades is not fully understood. Aside from their classical role as cofactors for PPO activation, we have previously revealed an unprecedented complexity in the function and molecular organization of these cSPHs in the immune response of the malaria vectorAnopheles gambiae. Here, we add yet another dimens...
Source: Journal of Innate Immunity - November 24, 2022 Category: Allergy & Immunology Source Type: research
IRF1 Is Required for MDA5 (IFIH1) Induction by IFN- α, LPS, and poly(I:C) in Murine Macrophages
Melanoma differentiation-associated protein 5 (MDA5) induces type I interferons (IFNs) after the recognition of viral RNA. In addition, gain-of-function mutations in the interferon induced with helicase C domain 1 (IFIH1) gene, which encodes MDA5, lead to type I interferonopathies. Here, we show thatMda5 is highly expressed in murine macrophages and is regulated by pro-inflammatory stimuli such as the cytokines IFN- α and IFN-γ, the TLR ligand LPS, and a mimic of dsRNA, poly(I:C).Mda5 induction is mediated through the production of reactive oxygen species. The induction by IFN- α or LPS occurs at the transcriptional lev...
Source: Journal of Innate Immunity - November 15, 2022 Category: Allergy & Immunology Source Type: research
GSK3 β Inhibition Prevents Macrophage Reprogramming by High-Dose Methotrexate
Methotrexate (MTX) is an antifolate drug used as a chemotherapeutic agent for acute lymphoblastic leukemia, where MTX improves patients ’ prognosis. Macrophage reprogramming is being increasingly assessed as an antitumor therapeutic strategy. However, and although MTX limits the pathogenic action of macrophages in chronic inflammatory diseases, its effects on tumor-promoting macrophages have not been previously explored. We now re port that MTX shapes the transcriptional and functional profile of M-CSF-dependent human macrophages, whose transcriptome is highly enriched in the gene signature that defines pathogenic tumor-...
Source: Journal of Innate Immunity - November 14, 2022 Category: Allergy & Immunology Source Type: research
MCPIP-1-Mediated Immunosuppression of Neutrophils Exacerbates Acute Bacterial Peritonitis and Liver Injury
Monocyte chemotactic protein-1-induced protein-1 (MCPIP-1) is highly expressed in activated immune cells and negatively regulates immune responses, while the mechanisms underlying the immunoregulation of neutrophils in acute bacterial infection and liver injury remain elusive. Here, we examined the role of MCPIP-1 in regulating neutrophil functions during acute bacterial peritonitis and liver injury. Mice with myeloid cell-specific overexpression (McpipMye-tg) or knockout (McpipΔMye) of MCPIP-1 were generated. We found that reactive oxygen species and myeloperoxidase production, formation of neutrophil extracellular traps...
Source: Journal of Innate Immunity - October 21, 2022 Category: Allergy & Immunology Source Type: research
