CD1a is a lipid-presenting molecule abundantly expressed on Langerhans cells. However, the in vivo role of CD1a remains unclear, principally because CD1a is lacking in mice. Using CD1a-transgenic mice, we show that the plant-derived lipid urushiol triggers CD1a-dependent skin inflammation, driven by CD4+ T cells producing IL-17 and IL-22. Human subjects with poison ivy dermatitis showed a similar cytokine signature following CD1a-mediated urushiol recognition. Among different urushiol congeners, we identified diunsaturated pentadecylcatechol (C15:2) as the dominant antigen for CD1a-restricted T cells. We determined the crystal structure of the CD1a-urushiol (C15:2) complex, demonstrating the molecular basis of urushiol interaction with the antigen-binding cleft of CD1a. In a mouse model and psoriasis patients, CD1a amplified inflammatory responses mediated by TH17 cells reactive with self lipid antigens. Treatment with blocking antibodies against CD1a alleviated skin inflammation. Thus, we propose CD1a as a potential therapeutic target in inflammatory skin diseases.

Following infection with certain strains of Shiga toxin-producing Escherichia coli (STEC), particularly enterohemorrhagic ones, patients are at elevated risk for developing life-threatening extraintestinal complications, such as acute renal failure. Hence, these bacteria represent a public health concern in both developed and developing countries. Shiga toxins (Stxs) expressed by STEC are highly cytotoxic class II ribosome-inactivating proteins and primary virulence factors responsible for major clinical signs of Stx-mediated pathogenesis, including bloody diarrhea, hemolytic uremic syndrome (HUS), and neurological complications. Ruminant animals are thought to serve as critical environmental reservoirs of Stx-producing Escherichia coli (STEC), but other emerging or arising reservoirs of the toxin-producing bacteria have been overlooked. In particular, a number of new animal species from wildlife and aquaculture industries have recently been identified as unexpected reservoir or spillover hosts of STEC. Here, we summarize recent findings about reservoirs of STEC and review outbreaks of these bacteria both within and outside the United States. A better understanding of environmental transmission to humans will facilitate the development of novel strategies for preventing zoonotic STEC infection.

No abstract