Staphylococcus aureus-specific skin resident memory T cells protect against bacteria colonization but exacerbate atopic dermatitis-like flares in mice.

BACKGROUND: The contribution of Staphylococcus aureus to the exacerbation of atopic dermatitis (AD) is widely documented, but its role as a primary trigger of AD skin symptoms remains poorly explored. OBJECTIVES: This study sought to reappraise the main bacterial factors and underlying immune mechanisms by which S aureus triggers AD-like inflammation. METHODS: This study capitalized on a preclinical model, in which different clinical isolates were applied in the absence of any prior experimental skin injury. RESULTS: The development of S aureus-induced dermatitis depended on the nature of the S aureus strain, its viability, the concentration of the applied bacterial suspension, the production of secreted and nonsecreted factors, as well as the activation of accessory gene regulatory quorum sensing system. In addition, the rising dermatitis, which exhibited the well-documented AD cytokine signature, was significantly inhibited in inflammasome adaptor apoptosis-associated speck-like protein containing a CARD domain- and monocyte/macrophage-deficient animals, but not in T- and B-cell-deficient mice, suggesting a major role for the innate response in the induction of skin inflammation. However, bacterial exposure generated a robust adaptive immune response against S aureus, and an accumulation of S aureus-specific γδ and CD4+ tissue resident memory T cells at the site of previous dermatitis. The latter both contributed to worsen the flares of AD-like dermatitis on new bacteria exposures, but also, protected the mice from persistent bacterial colonization. CONCLUSIONS: These data highlight the induction of unique AD-like inflammation, with the generation of proinflammatory but protective tissue resident memory T cells in a context of natural exposure to pathogenic S aureus strains.

Polyclonal expansion of TCR Vbeta 21.3+ CD4+ and CD8+ T cells is a hallmark of Multisystem Inflammatory Syndrome in Children.

Multiple Inflammatory Syndrome in Children (MIS-C) is a delayed and severe complication of SARS-CoV-2 infection that strikes previously healthy children. As MIS-C combines clinical features of Kawasaki disease and Toxic Shock Syndrome (TSS), we aimed to compare the immunological profile of pediatric patients with these different conditions. We analyzed blood cytokine expression, and the T cell repertoire and phenotype in 36 MIS-C cases, which were compared to 16 KD, 58 TSS, and 42 COVID-19 cases. We observed an increase of serum inflammatory cytokines (IL-6, IL-10, IL-18, TNF-α, IFNγ, CD25s, MCP1, IL-1RA) in MIS-C, TSS and KD, contrasting with low expression of HLA-DR in monocytes. We detected a specific expansion of activated T cells expressing the Vß21.3 T cell receptor ß chain variable region in both CD4 and CD8 subsets in 75% of MIS-C patients and not in any patient with TSS, KD, or acute COVID-19; this correlated with the cytokine storm detected. The T cell repertoire returned to baseline within weeks after MIS-C resolution. Vß21.3+ T cells from MIS-C patients expressed high levels of HLA-DR, CD38 and CX3CR1 but had weak responses to SARS-CoV-2 peptides in vitro. Consistently, the T cell expansion was not associated with specific classical HLA alleles. Thus, our data suggested that MIS-C is characterized by a polyclonal Vß21.3 T cell expansion not directed against SARS-CoV-2 antigenic peptides, which is not seen in KD, TSS and acute COVID-19.

Susceptibility trends including emergence of linezolid resistance among coagulase-negative staphylococci and meticillin-resistant Staphylococcus aureus from invasive infections.

Multiresistance in staphylococci constitutes a major challenge for the antimicrobial chemotherapy of invasive infections such as bacteraemia or bone and joint infections (BJIs). A nationwide prospective study was performed to detect antimicrobial resistance trends among staphylococci causing invasive infections. Between October 2011 and February 2012, 367 meticillin-resistant Staphylococcus aureus (MRSA) and 695 coagulase-negative staphylococci (CoNS) were collected from 37 French hospitals, mainly from bacteraemia (59.9%) and osteoarticular infections (29.0%). Minimum inhibitory concentrations (MICs) were determined by broth microdilution, and specific screening and confirmation tests were performed to detect heterogeneous vancomycin-intermediate S. aureus (hVISA). Staphylococcal isolates exhibiting a linezolid MIC>4 mg/L were further characterised to determinate their clonal relationships and the mechanism of resistance. MRSA exhibited additional resistances, including levofloxacin (82% associated resistance), gentamicin (13.6%), fusidic acid (13.6%) and rifampicin (6.5%), compromising oral step-down therapy in BJIs. Only two hVISA strains (0.5%) were identified. Among the CoNS, mainly Staphylococcus epidermidis (506/695; 72.8%), resistance to first- and second-line agents was more common. Linezolid resistance was identified in 10 CoNS (1.4%). The most frequent linezolid resistance mechanism was the G2576T mutation in 23S rDNA (9/10). For the first time in France, the cfr gene was found in five related sequence type 2 (ST2) S. epidermidis from two different hospitals, in association with ribosomal RNA and L3 ribosomal protein mutations. These national data must be considered when selecting empirical treatment for invasive staphylococcal infections. Moreover, the emergence and spread of linezolid-resistant CoNS carrying the cfr gene is of concern.