No abstract

The origin of extant amphibians (Lissamphibia: frogs, salamanders and caecilians) is one of the most controversial questions in vertebrate evolution, owing to large morphological and temporal gaps in the fossil record. Current discussions focus on three competing hypotheses: a monophyletic origin within either Temnospondyli or Lepospondyli, or a polyphyletic origin with frogs and salamanders arising among temnospondyls and caecilians among the lepospondyls. Recent molecular analyses are also controversial, with estimations for the batrachian (frog-salamander) divergence significantly older than the palaeontological evidence supports. Here we report the discovery of an amphibamid temnospondyl from the Early Permian of Texas that bridges the gap between other Palaeozoic amphibians and the earliest known salientians and caudatans from the Mesozoic. The presence of a mosaic of salientian and caudatan characters in this small fossil makes it a key taxon close to the batrachian (frog and salamander) divergence. Phylogenetic analysis suggests that the batrachian divergence occurred in the Middle Permian, rather than the late Carboniferous as recently estimated using molecular clocks, but the divergence with caecilians corresponds to the deep split between temnospondyls and lepospondyls, which is congruent with the molecular estimates.

No abstract

Tuned and distinct responses of macrophages and dendritic cells to Toll-like receptor 4 (TLR4) activation induced by lipopolysaccharide (LPS) underpin the balance between innate and adaptive immunity. However, the molecule(s) that confer these cell-type-specific LPS-induced effects remain poorly understood. Here we report that the integrin αM (CD11b) positively regulates LPS-induced signalling pathways selectively in myeloid dendritic cells but not in macrophages. In dendritic cells, which express lower levels of CD14 and TLR4 than macrophages, CD11b promotes MyD88-dependent and MyD88-independent signalling pathways. In particular, in dendritic cells CD11b facilitates LPS-induced TLR4 endocytosis and is required for the subsequent signalling in the endosomes. Consistent with this, CD11b deficiency dampens dendritic cell-mediated TLR4-triggered responses in vivo leading to impaired T-cell activation. Thus, by modulating the trafficking and signalling functions of TLR4 in a cell-type-specific manner CD11b fine tunes the balance between adaptive and innate immune responses initiated by LPS.

No abstract