We identified B cells as a major source for rapid, innate-like interleukin 17 (IL-17) production in vivo in response to Trypanosoma cruzi infection. IL-17+ B cells exhibited a plasmablast phenotype, outnumbered TH17 cells and were required for optimal response to this pathogen. Using both murine and human primary B cells, we demonstrate that exposure to parasite-derived trans-sialidase in vitro was sufficient to trigger modification of the cell surface mucin, CD45, leading to Btk-dependent signaling and IL-17A or IL-17F production via an ROR-γt and AHR-independent transcriptional program. Our combined data suggest that generation of IL-17+ B cells may be an unappreciated feature of innate immune responses required for pathogen control or IL-17-mediated autoimmunity.

Polymorphisms of interleukin (IL)-23R and signaling components are associated with several autoimmune diseases, including inflammatory bowel diseases (IBD). Similar to T helper type 17 (Th17) lineage, type 3 innate lymphoid cells (ILCs) express retinoic acid–related orphan receptor γt (Rorγt) and IL-23R and hence, produce Th17-type cytokines. Recent reports implicated type 3 ILCs in IBD; however, how IL-23R signaling in these cells contributes to pathogenesis is unknown. IL-22, produced in copious amounts by type 3 ILCs, was reported to have both beneficial and pathogenic effects in adaptive, yet only a protective role in innate colitis models. Herein, by employing chronic CD45RBhigh CD4+ T-cell transfer and anti-CD40 antibody-induced acute innate colitis models in Rag1−/− mice, wedemonstrated opposite roles for IL-23R in colitogenesis: in the former a protective, and in the latter a pathogenic role. Furthermore, we show that IL-23R signaling promotes innate colitis via IL-22 as neutralization of IL-22 protected mice from colitis and adding back of IL-22 to IL-23R-deficient animals restored the disease. Collectively, our results reveal that similar to its controversial role during chronic or adaptive colitis, IL-22 may also have opposite roles in innate colitis pathogenesis in a context and insult-dependent manner.

BLM, the protein mutated in Bloom's syndrome, possesses a helicase activity that can dissociate DNA structures, including the Holliday junction, expected to arise during homologous recombination. BLM is stably associated with topoisomerase III␣ (Topo III␣) and the BLAP75 protein. The BLM-Topo III␣-BLAP75 (BTB) complex can efficiently resolve a DNA substrate that harbors two Holliday junctions (the double Holliday junction) in a non-crossover manner. Here we show that the Holliday junction unwinding activity of BLM is greatly enhanced as a result of its association with Topo III␣ and BLAP75. Enhancement of this BLM activity requires both Topo III␣ and BLAP75. Importantly, Topo III␣ cannot be substituted by Escherichia coli Top3, and the Holliday junction unwinding activity of BLMrelated helicases WRN and RecQ is likewise impervious to Topo III␣ and BLAP75. However, the topoisomerase activity of Topo III␣ is dispensable for the enhancement of the DNA unwinding reaction. We have also ascertained the requirement for the BLM ATPase activity in double Holliday junction dissolution and DNA unwinding by constructing, purifying, and characterizing specific mutant variants that lack this activity. These results provide valuable information concerning how the functional integrity of the BTB complex is governed by specific protein-protein interactions among the components of this complex and the enzymatic activities of BLM and Topo III␣. Homologous recombination (HR)3 is important for several nuclear processes, including the repair of damaged DNA, rescue of stalled DNA replication forks, and pairing of homologous chromosomes during meiosis. HR can produce recombinant chromosomes that harbor a crossover of the chromosomal arms. Although these crossovers are critical for the proper segregation of homologous chromosomes in meiosis I (1), inadvertent crossover formation in mitotic cells can lead to chromosome translocation and loss of heterozygosity, which are potentially oncogenic (2-6). For this reason, eukaryotes have developed specific mechanisms for suppressing the formation of DNA crossovers in mitotic cells (7-9).Several members of the RecQ helicase family have been implicated in mitotic crossover suppression (reviewed in 10 -12). BLM, the protein mutated in the autosomal recessive cancer-predisposing disorder Bloom's syndrome (BS), is one of the five members of the RecQ helicase family in humans (13,14). Cells from the patients with BS display a high degree of genomic instability (15, 16) and a dramatic increase in the frequency of sister chromatid exchanges mediated by HR (16,17). BLM is thought to prevent crossover formation by (i) promoting the synthesis-dependent single strand annealing pathway of HR by dissociating the D-loop structure, an intermediate formed early in the HR reaction, and (ii) acting in conjunction with additional protein factors to dissolve the double-Holliday junction (DHJ), a late HR intermediate, to generate solely noncrossover recombinants (18 -20). BLM has also been proposed to function in th...

The complement system is a potent innate immune mechanism consisting of cascades of proteins which are designed to fight against and annul intrusion of all the foreign pathogens. Although viruses are smaller in size and have relatively simple structure, they are not immune to complement attack. Thus, activation of the complement system can lead to neutralization of cell-free viruses, phagocytosis of C3b-coated viral particles, lysis of virus-infected cells, and generation of inflammatory and specific immune responses. However, to combat host responses and succeed as pathogens, viruses not only have developed/adopted mechanisms to control complement, but also have turned these interactions to their own advantage. Important examples include poxviruses, herpesviruses, retroviruses, paramyxoviruses and picornaviruses. In this review, we provide information on the various complement evasion strategies that viruses have developed to thwart the complement attack of the host. A special emphasis is given on the interactions between the viral proteins that are involved in molecular mimicry and the complement system.