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Antibiotic exposure near the time of birth reduces the diversity and composition of intestinal microbiota and delays the appearance of beneficial bacteria in children (4); such alterations are associated with [...], Neonatal colonization by microbes, which begins immediately after birth, is influenced by gestational age and the mother's microbiota and is modified by exposure to antibiotics (1). In neonates, prolonged duration of antibiotic therapy is associated with increased risk of late-onset sepsis (LOS) (2), a disorder controlled by neutrophils (3). A role for the microbiota in regulating neutrophil development and susceptibility to sepsis in the neonate remains unclear. We exposed pregnant mouse dams to antibiotics in drinking water to limit transfer of maternal microbes to the neonates. Antibiotic exposure of dams decreased the total number and composition of microbes in the intestine of the neonates. This was associated with decreased numbers of circulating and bone marrow neutrophils and granulocyte/macrophage-restricted progenitor cells in the bone marrow of antibiotic-treated and germ-free neonates. Antibiotic exposure of dams reduced the number of interleukin-17 (IL-17)-producing cells in the intestine and production of granulocyte colony-stimulating factor (G-CSF). Granulocytopenia was associated with impaired host defense and increased susceptibility to Escherichia coli K1 and Klebsiella pneumoniae sepsis in antibiotic-treated neonates, which could be partially reversed by administration of G-CSF. Transfer of a normal microbiota into antibiotic-treated neonates induced IL-17 production by group 3 innate lymphoid cells (ILCs) in the intestine, increasing plasma G-CSF levels and neutrophil numbers in a Toll-like receptor 4 (TLR4)-and myeloid differentiation factor 88 (MyD88)-dependent manner and restored IL-17-dependent resistance to sepsis. Specific depletion of ILCs prevented IL-17-and G-CSF-dependent granulocytosis and resistance to sepsis. These data support a role for the intestinal microbiota in regulation of granulocytosis, neutrophil homeostasis and host resistance to sepsis in neonates.

Although nontyphoidal Salmonella serotypes (NTS) are common agents causing acute food-borne disease worldwide, it is unusual to isolate them from the blood of adults, because in immunocompetent individuals these pathogens [...], Salmonella typhimurium causes a localized enteric infection in immunocompetent individuals, whereas HIV-infected individuals develop a life-threatening bacteremia. Here we show that simian immunodeficiency virus (SIV) infection results in depletion of T helper type 17 ([T.sub.H]17) cells in the ileal mucosa of rhesus macaques, thereby impairing mucosal barrier functions to S. typhimurium dissemination. In SIV-negative macaques, the gene expression profile induced by S. typhimurium in ligated ileal loops was dominated by [T.sub.H]17 responses, including the expression of interleukin-17 (IL-17) and IL-22. [T.sub.H]17 cells were markedly depleted in SIV-infected rhesus macaques, resulting in blunted [T.sub.H]17 responses to S. typhimurium infection and increased bacterial dissemination. IL-17 receptor-deficient mice showed increased systemic dissemination of S. typhimurium from the gut, suggesting that IL-17 deficiency causes defects in mucosal barrier function. We conclude that SIV infection impairs the IL-17 axis, an arm of the mucosal immune response preventing systemic microbial dissemination from the gastrointestinal tract.

IL-17 is a proinflammatory cytokine implicated in many autoimmune disease (1-3). Recently, it has been shown that IL-17-producing T cells belong to a unique subset of T cells, [T.sub.H]17 cells, [...], Emerging evidence supports the concept that T helper type 17 ([T.sub.H]17) cells, in addition to mediating autoimmunity, have key roles in mucosal immunity against extracellular pathogens. Interleukin-22 (IL-22) and IL-17A are both effector cytokines produced by the [T.sub.H]17 lineage, and both were crucial for maintaining local control of the Gram-negative pulmonary pathogen, Klebsiella pneumoniae. Although both cytokines regulated CXC chemokines and granulocyte colony-stimulating factor production in the lung, only IL-22 increased lung epithelial cell proliferation and increased transepithelial resistance to injury. These data support the concept that the [T.sub.H]17 cell lineage and its effector molecules have evolved to effect host defense against extracellular pathogens at mucosal sites.

Bacterial pneumonia can be a life-threatening disease that causes lung injury. A new study shows that accumulation of a phospholipid in the lung fluid in mice and humans worsens gas [...]