Streptococcus agalactiae and Escherichia coli Induce Distinct Effector γδ T Cell Responses During Neonatal Sepsis.

Neonates born prematurely are highly vulnerable to life-threatening conditions such as bacterial sepsis. Streptococcus agalactiae, also known as group B Streptococcus (GBS) and Escherichia coli are frequent causative pathogens of neonatal sepsis, however, it remains unclear if distinct sepsis pathogens induce differential adaptive immune responses. In the present study, we find that γδ T cells in neonatal mice rapidly respond to single-organism GBS and E. coli bloodstream infections and that these pathogens induce distinct activation and cytokine production from IFN-γ and IL-17 producing γδ T cells, respectively. We also report differential reliance on γδTCR signaling to elicit effector cytokine responses during neonatal sepsis, with IL-17 production during E. coli infection being driven by γδTCR signaling, and IFN-γ production during GBS infection occurring independently of γδTCR signaling. Furthermore, we report that the divergent effector responses of γδ T cells during GBS and E. coli infections impart distinctive neuroinflammatory phenotypes on the neonatal brain. The present study reveals that the neonatal adaptive immune system differentially responds to distinct bacterial stimuli, resulting in unique neuroinflammatory phenotypes.

Streptococcus agalactiae and Escherichia coli induce distinct effector γδ T cell responses during neonatal sepsis.

Neonates born prematurely are vulnerable to life-threatening conditions such as bacterial sepsis. Streptococcus agalactiae (GBS) and Escherichia coli are frequent causative pathogens of neonatal sepsis, however, it remains unclear if these pathogens induce differential immune responses. We find that γδ T cells rapidly respond to single-organism GBS and E. coli bloodstream infections in neonatal mice. Furthermore, GBS and E. coli induce distinct cytokine production from IFN-γ and IL-17 producing γδ T cells, respectively. We also find that IL-17 production during E. coli infection is driven by γδTCR signaling, whereas IFN-γ production during GBS infection occurs independently of γδTCR signaling. The divergent effector responses of γδ T cells during GBS and E. coli infections impart distinctive neuroinflammatory phenotypes on the neonatal brain. Thus, the neonatal adaptive immune system differentially responds to distinct bacterial stimuli, resulting in unique neuroinflammatory phenotypes.

Neonatal intestinal colonization of Streptococcus agalactiae and the multiple modes of protection limiting translocation.

Streptococcus agalactiae, also known as Group B Streptococcus (GBS), is a predominant pathogen of neonatal sepsis, commonly associated with early-onset neonatal sepsis. GBS has also been associated with cases of late-onset sepsis potentially originating from the intestine. Previous findings have shown GBS can colonize the infant intestinal tract as part of the neonatal microbiota. To better understand GBS colonization dynamics in the neonatal intestine, we collected stool and milk samples from prematurely born neonates for identification of potential pathogens in the neonatal intestinal microbiota. GBS was present in approximately 10% of the cohort, and this colonization was not associated with maternal GBS status, delivery route, or gestational weight. Interestingly, we observed the relative abundance of GBS in the infant stool negatively correlated with maternal IgA concentration in matched maternal milk samples. Using a preclinical murine model of GBS infection, we report that both vertical transmission and direct oral introduction resulted in intestinal colonization of GBS; however, translocation beyond the intestine was limited. Finally, vaccination of dams prior to breeding induced strong immunoglobulin responses, including IgA responses, which were associated with reduced mortality and GBS intestinal colonization. Taken together, we show that maternal IgA may contribute to infant immunity by limiting the colonization of GBS in the intestine.

Lung Ultrasound versus Chest X-Ray for the Detection of Fluid Overload in Critically Ill Children: A Systematic Review.

Fluid overload is a common complication of critical illness, associated with increased morbidity and mortality. Pulmonary fluid status is difficult to evaluate clinically and many clinicians utilize chest X-ray (CXR) to identify fluid overload. Adult data have shown lung ultrasound (LUS) to be a more sensitive modality. Our objective was to determine the performance of LUS for detecting fluid overload, with comparison to CXR, in critically ill children. We conducted a systematic review using multiple electronic databases and included studies from inception to November 15, 2020. The sensitivity and specificity of each test were evaluated. Out of 1,209 studies screened, 4 met eligibility criteria. Overall, CXR is reported to have low sensitivity (44-58%) and moderate specificity (52-94%) to detect fluid overload, while LUS is reported to have high sensitivity (90-100%) and specificity (94-100%). Overall, the quality of evidence was moderate, and the gold standard was different in each study. Our systematic review suggests LUS is more sensitive and specific than CXR to identify pulmonary fluid overload in critically ill children. Considering the clinical burden of fluid overload and the relative ease of obtaining LUS, further evaluation of LUS to diagnose volume overload is warranted.

Sepsis, Cytokine Storms, and Immunopathology: The Divide between Neonates and Adults.

Sepsis can result from a variety of pathogens, originating from a range of sources. A vast range of presenting symptoms is included in the catch-all term of "bacteremia," making diagnosis and prognosis particularly troublesome. One underexplored factor contributing to disparate outcomes is the age of the patient. Neonatal sepsis in very-low-birth-weight infants can result in vastly different immunological outcomes unique from sepsis in adults. It is also becoming increasingly clear, both from preclinical experimental models and clinical observations, that the age and history of previous microbial exposures can significantly influence the course of infection from sepsis and cytokine storms to immunopathology. In this study, we will explore key differences between neonatal and adult sepsis, experimental models used to study sepsis, and how responses to the surrounding microbial universe shape development of the immune system and impact, positively or negatively, the course of disease.

Brighter Days May Be Ahead: Continuous Measurement of Pediatric Intensive Care Unit Light and Sound.

Objective: To describe light and sound characteristics in the rooms of critically ill children. Design: Prospective observational cohort study, with continuously measured light and sound levels. Setting: Tertiary care pediatric intensive care unit (PICU), with a newly constructed expansion and an older, pre-existing section. Patients: Critically ill patients 0-18 years old, requiring respiratory or cardiovascular support. Patients with severe cognitive pre-conditions were excluded. Measurements and Main Results: One hundred patients were enrolled, totaling 602 patient-days. The twenty-four hour median illuminance was 16 (IQR 5-53) lux (lx). Daytime (07:00-21:00) median light level was 27 lx (IQR 13-82), compared with 4 lx (IQR 1-10) overnight (22:00-06:00). Peak light levels occurred midday between 11:00 and 14:00, with a median of 48 lx (IQR 24-119). Daytime median illuminance trended higher over the course of admission, whereas light levels overnight were consistent. Midday light levels were higher in newly constructed rooms: 78 lx (IQR 30-143) vs. 26 lx (IQR 20-40) in existing rooms. The twenty-four hour median equivalent sound level (LAeq) was 60 (IQR 55-64) decibels (dB). Median daytime LAeq was 62 dB (IQR 58-65) and 56 dB (IQR 52-61) overnight. On average, 35% of patients experienced at least one sound peak >80 dB every hour from 22:00 to 06:00. Overnight peaks, but not median sound levels nor daytime peaks, decreased over the course of admission. There was no difference in sound between new and pre-existing rooms. Conclusions: This study describes continuously measured light and sound in PICU rooms. Light levels were low even during daytime hours, while sound levels were consistently higher than World Health Organization hospital room recommendations of <35 dB. Given the relevance of light and sound to sleep/wake patterns, and evidence of post-intensive care syndromes, the clinical effects of light and sound on critically ill children should be further explored as potentially modifiable environmental factors.