The gut microbiota in early life, when critical immune maturation takes place, may influence the immunogenicity of childhood vaccinations. Here we assess the association between mode of delivery, gut ...microbiota development in the first year of life, and mucosal antigen-specific antibody responses against pneumococcal vaccination in 101 infants at age 12 months and against meningococcal vaccination in 66 infants at age 18 months. Birth by vaginal delivery is associated with higher antibody responses against both vaccines. Relative abundances of vaginal birth-associated Bifidobacterium and Escherichia coli in the first weeks of life are positively associated with anti-pneumococcal antibody responses, and relative abundance of E. coli in the same period is also positively associated with anti-meningococcal antibody responses. In this study, we show that mode of delivery-induced microbiota profiles of the gut are associated with subsequent antibody responses to routine childhood vaccines.
This study reveals that 1918 H1N1 influenza virus spreads to and induces proinflammatory cytokine responses in extrarespiratory tissues, including the nervous system, liver, and heart. This likely ...contributes to the development of severe disease, including diseases of the nervous system.
Abstract
Background
The 1918 Spanish H1N1 influenza pandemic was the most severe recorded influenza pandemic with an estimated 20–50 million deaths worldwide. Even though it is known that influenza viruses can cause extrarespiratory tract complications—which are often severe or even fatal—the potential contribution of extrarespiratory tissues to the pathogenesis of 1918 H1N1 virus infection has not been studied comprehensively.
Methods
Here, we performed a time-course study in ferrets inoculated intranasally with 1918 H1N1 influenza virus, with special emphasis on the involvement of extrarespiratory tissues. Respiratory and extrarespiratory tissues were collected after inoculation for virological, histological, and immunological analysis.
Results
Infectious virus was detected at high titers in respiratory tissues and, at lower titers in most extrarespiratory tissues. Evidence for active virus replication, as indicated by the detection of nucleoprotein by immunohistochemistry, was observed in the respiratory tract, peripheral and central nervous system, and liver. Proinflammatory cytokines were up-regulated in respiratory tissues, olfactory bulb, spinal cord, liver, heart, and pancreas.
Conclusions
1918 H1N1 virus spread to and induced cytokine responses in tissues outside the respiratory tract, which likely contributed to the severity of infection. Moreover, our data support the suggested link between 1918 H1N1 infection and central nervous system disease.
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