The Influence of Antibiotic Resistance on Innate Immune Responses to Staphylococcus aureus Infection.

Staphylococcus aureus (S. aureus) causes a broad range of infections and is associated with significant morbidity and mortality. S. aureus produces a diverse range of cellular and extracellular factors responsible for its invasiveness and ability to resist immune attack. In recent years, increasing resistance to last-line anti-staphylococcal antibiotics daptomycin and vancomycin has been observed. Resistant strains of S. aureus are highly efficient in invading a variety of professional and nonprofessional phagocytes and are able to survive inside host cells. Eliciting immune protection against antibiotic-resistant S. aureus infection is a global challenge, requiring both innate and adaptive immune effector mechanisms. Dendritic cells (DC), which sit at the interface between innate and adaptive immune responses, are central to the induction of immune protection against S. aureus. However, it has been observed that S. aureus has the capacity to develop further antibiotic resistance and acquire increased resistance to immunological recognition by the innate immune system. In this article, we review the strategies utilised by S. aureus to circumvent antibiotic and innate immune responses, especially the interaction between S. aureus and DC, focusing on how this relationship is perturbed with the development of antibiotic resistance.

Discordance in STING-Induced Activation and Cell Death Between Mouse and Human Dendritic Cell Populations.

Stimulator of Interferon Genes (STING) is a cytosolic sensor of cyclic dinucleotides (CDNs). The activation of dendritic cells (DC) via the STING pathway, and their subsequent production of type I interferon (IFN) is considered central to eradicating tumours in mouse models. However, this contribution of STING in preclinical murine studies has not translated into positive outcomes of STING agonists in phase I & II clinical trials. We therefore questioned whether a difference in human DC responses could be critical to the lack of STING agonist efficacy in human settings. This study sought to directly compare mouse and human plasmacytoid DCs and conventional DC subset responses upon STING activation. We found all mouse and human DC subsets were potently activated by STING stimulation. As expected, Type I IFNs were produced by both mouse and human plasmacytoid DCs. However, mouse and human plasmacytoid and conventional DCs all produced type III IFNs (i.e., IFN-λs) in response to STING activation. Of particular interest, all human DCs produced large amounts of IFN-λ1, not expressed in the mouse genome. Furthermore, we also found differential cell death responses upon STING activation, observing rapid ablation of mouse, but not human, plasmacytoid DCs. STING-induced cell death in murine plasmacytoid DCs occurred in a cell-intrinsic manner and involved intrinsic apoptosis. These data highlight discordance between STING IFN and cell death responses in mouse and human DCs and caution against extrapolating STING-mediated events in mouse models to equivalent human outcomes.

Changing Trend of Superficial Mycoses with Increasing Nondermatophyte Mold Infection: A Clinicomycological Study at a Tertiary Referral Center in Assam.

BACKGROUND: Superficial mycosis is the commonest infections affecting human globally. Though they do not cause mortality, their clinical significance lies in their morbidity, recurrence, and cosmetic disfigurement, thus creating a major public health problem. The infections are more prevalent in the tropical regions. The etiological agents are also seen to vary with time and geographical location. AIM: This study was carried out to find out the trend of superficial mycosis in Assam, along with a clinicomycological correlation. MATERIALS AND METHODS: A total of 130 clinically diagnosed cases of superficial mycoses attending the outpatient department (OPD) of a tertiary hospital in Assam for a period of 1 year were taken up for the study. After taking the informed consent and a proper history, the clinical materials like skin scrapings, nail clippings, and infected hair were sent for mycological examination. RESULTS: The infection was found to be more prevalent among males than females (M:F, 3:2) and among the farmers and laborers (24.61%). Tinea corporis was the commonest clinical type (21.5%). Among the fungal isolates, dermatophytes were the most frequent isolates (43.54%), out of which Trichophyton rubrum was commonest. nondermatophyte moulds like Fusarium, Aspergillus, Scopulariopsis, Trichosporon, and Penicillium spp. were isolated. CONCLUSION: The epidemiology of fungal infection and the causative fungi is seen to vary geographically and with time. This study reflects the changing trend of fungal infection in the north eastern region with a high rate of isolation of nondermatophyte moulds as the causative agent.