Group B Streptococci remain one of the main causes of invasive neonatal infections, which usually manifest as sepsis, meningitis, or pneumonia. To date, 10 different serotypes (Ia, Ib, II – IX) have been described, which differ in their virulence and the immune response they trigger. Since intrapartum antibiotic prophylaxis is only effective in preventing an early onset of the disease, further research into GBS-associated pathogenesis is needed. Using various immunological, microscopic and genetic methods, we have investigated how genotypic and phenotypic differences between GBS isolates affect the innate immune response of macrophages at multiple levels, from phagocytic uptake to phenotyping, cytokine production, cell death and metabolic changes. Significant isolate-specific differences were observed at all levels of macrophage response. Our data also suggest that different isolates have different potential to become invasive or remain colonizing. We have further shown that different isolates induce different levels of inflammatory responses and that individual isolates strongly induce inflammatory cell death, pyroptosis. Furthermore, differences in macrophage metabolism, which is crucial for proper effector functions of immune cells, were also observed for the first time. Our data suggest that the severity of the disease depends not only on the immune status of the individual but also on the isolate itself, as infection with different isolates leads to significant differences in the immune response of macrophages. The data obtained could prove useful for diagnostic purposes in the future, whereby the bacterial isolate itself could be used to deduce the prognosis of the disease.
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