A fungal metabolic regulator underlies infectious synergism during - aureus intra-abdominal co-infection.

and are two commonly associated pathogens that cause nosocomial infections with high morbidity and mortality. Our prior and current work using a murine model of polymicrobial intra-abdominal infection (IAI) uncovered synergistic lethality that was driven by -induced upregulation of functional ⍺-toxin leading to polymicrobial sepsis and organ damage. In order to determine the candidal effector(s) mediating enhanced virulence, an unbiased screen of transcription factor mutants was undertaken and revealed that Δ/Δ failed to drive augmented ⍺-toxin or lethal synergism during co-infection.

Protection against lethal sepsis following immunization with species varies by isolate and inversely correlates with bone marrow tissue damage.

Protection against lethal ()/ () intra-abdominal infection (IAI)-mediated sepsis can be achieved by a novel form of trained innate immunity (TII) involving Gr-1+ myeloid-derived suppressor cells (MDSCs) that are induced by inoculation (immunization) with low virulence species [i.e., ()] that infiltrate the bone marrow (BM).

-induced granulocytic myeloid-derived suppressor cells are protective against polymicrobial sepsis.

Polymicrobial intra-abdominal infections are serious clinical infections that can lead to life-threatening sepsis, which is difficult to treat in part due to the complex and dynamic inflammatory responses involved. Our prior studies demonstrated that immunization with low-virulence species can provide strong protection against lethal polymicrobial sepsis challenge in mice. This long-lived protection was found to be mediated by trained Gr-1 polymorphonuclear leukocytes with features resembling myeloid-derived suppressor cells (MDSCs).

Effect of MMR Vaccination to Mitigate Severe Sequelae Associated With COVID-19: Challenges and Lessons Learned.

Mortality in COVID-19 cases was strongly associated with progressive lung inflammation and eventual sepsis. There is mounting evidence that live attenuated vaccines commonly administered during childhood, also provide beneficial non-specific immune effects, including reduced mortality and hospitalization due to unrelated infections. It has been proposed that live attenuated vaccine-associated non-specific effects are a result of inducing trained innate immunity to function more effectively against broader infections.