Age-dependent natural killer cell and interferon γ deficits contribute to severe pertussis in infant mice.

Many respiratory infections are selectively injurious to infants, yet the etiology of age-associated susceptibility is unknown. One such bacterial pathogen is Bordetella pertussis. In adult mice, innate interferon γ (IFN-γ) is produced by natural killer (NK) cells and restricts infection to the respiratory tract. In contrast, infant pertussis resembles disease in NK cell- and IFN-γ-deficient adult mice that experience disseminated lethal infection. We hypothesized that infants exhibit age-associated deficits in NK cell frequency, maturation, and responsiveness to B. pertussis, associated with low IFN-γ levels. To delineate mechanisms behind age-dependent susceptibility, we compared infant and adult mouse models of infection. Infection in infant mice resulted in impaired upregulation of IFN-γ and substantial bacterial dissemination. B. pertussis-infected infant mice displayed fewer pulmonary NK cells than adult mice. Furthermore, the NK cells in the infant mouse lungs had an immature phenotype, and the infant lung showed no upregulation of the IFN-γ-inducing cytokine IL-12p70. Adoptive transfer of adult NK cells into infants, or treatment with exogenous IFN-γ, significantly reduced bacterial dissemination. These data indicate that the lack of NK cell-produced IFN-γ significantly contributes to infant fulminant pertussis and could be the basis for other pathogen-induced, age-dependent respiratory diseases.

In a wild germinal center, what determines survival of the fittest?

Mice with natural BCR frequencies have plasma cells enriched for high-affinity clones, but high-affinity clones persist in the germinal center, leaving the rules for plasma cell selection still murky.

Identification of the Fc-alpha/mu receptor in Xenopus provides insight into the emergence of the poly-Ig receptor (pIgR) and mucosal Ig transport.

The polyimmunoglobulin receptor (pIgR) transcytoses J chain-containing antibodies through mucosal epithelia. In mammals, two cis-duplicates of PIGR, FCMR, and FCAMR, flank the PIGR gene. A PIGR duplication is first found in amphibians, previously annotated as PIGR2 (herein xlFCAMR), and is expressed by APCs. We demonstrate that xlFcamR is the equivalent of mammalian FcamR. It has been assumed that pIgR is the oldest member of this family, yet our data could not distinguish whether PIGR or FCAMR emerged first; however, FCMR was the last family member to emerge. Interestingly, bony fish "pIgR" is not an orthologue of tetrapod pIgR, and possibly acquired its function via convergent evolution. PIGR/FCAMR/FCMR are members of a larger superfamily, including TREM, CD300, and NKp44, which we name the "double-disulfide Ig superfamily" (ddIgSF). Domains related to each ddIgSF family were identified in cartilaginous fish (sharks, chimeras) and encoded in a single gene cluster syntenic to the human pIgR locus. Thus, the ddIgSF families date back to the earliest antibody-based adaptive immunity, but apparently not before. Finally, our data strongly suggest that the J chain arose in evolution only for Ig multimerization. This study provides a framework for further studies of pIgR and the ddIgSF in vertebrates.

Near-Complete Sequence of a Highly Divergent Reovirus Genome Recovered from Callinectes sapidus.

This report describes the sequence of a reovirus genome, discovered in Callinectes sapidus in Brazil. The genome sequence of Callinectes sapidus reovirus 2 (CsRV2) consists of 12 segments that encode 13 putative proteins. The predicted RNA-dependent RNA polymerase is highly similar to that of Eriocheir sinensis reovirus 905, suggesting that CsRV2 also belongs to the genus Cardoreovirus.

Prevalence of the pathogenic crustacean virus Callinectes sapidus reovirus 1 near flow-through blue crab aquaculture in Chesapeake Bay, USA.

Understanding the ecology of diseases is important to understanding variability in abundance, and therefore management, of marine animals exploited commercially. The blue crab Callinectes sapidus fills a crucial benthic-pelagic niche in Atlantic estuarine ecosystems and supports large commercial fisheries in both North and South America. In the USA, pre-molt blue crabs are typically held in short-term shedding (ecdysis) facilities to produce soft-shell crabs of increased value. However, mortality rates in these facilities are high and commonly associated with the pathogenic C. sapidus reovirus 1 (CsRV1). To assess whether crab mortalities in these facilities might increase CsRV1 prevalence in wild crab populations, tissue sampled from crabs collected over 2 summers either near to or far from shedding facilities using flow-through water systems were tested by reverse transcription quantitative PCR (RT-qPCR) for the presence of CsRV1 RNA. In support of our hypothesis, PCR data identified the probability of detecting CsRV1 in wild crabs sampled close to shedding facilities to be 78% higher than in crabs sampled from far sites. PCR detections were also 61-72% more probable in male crabs and 21% more likely in male and female crabs over the minimum landing size. As the prevalence at which CsRV1 was detected varied within seasons, among locations and between years, blue crab migration and/or population fluctuations appear to also be involved.

"Double-duty" conventional dendritic cells in the amphibian Xenopus as the prototype for antigen presentation to B cells.

Two populations of dendritic cells (DCs) are found in mammals, one derived from hematopoietic precursors (conventional/cDC), and another derived from mesenchymal precursors, the follicular DC (FDC); the latter is specialized for antigen presentation to B cells, and has only been definitively demonstrated in mammals. Both cDC and FDC are necessary for induction of germinal centers (GC) and GC-dependent class switch recombination (CSR) and somatic hypermutation (SHM). We demonstrate that in Xenopus, an amphibian in which immunoglobulin CSR and SHM occur without GC formation, a single type of DC has properties of both cDC and FDC, including high expression of MHC class II for the former and display of native antigen at the cell surface for the latter. Our data confirm that the advent of FDC functionality preceded emergence of bona fide FDC, which was in turn crucial for the development of GC formation and efficient affinity maturation in mammals.

Genome Sequence Analysis of CsRV1: A Pathogenic Reovirus that Infects the Blue Crab Callinectes sapidus Across Its Trans-Hemispheric Range.

The blue crab, Callinectes sapidus Rathbun, 1896, which is a commercially important trophic link in coastal ecosystems of the western Atlantic, is infected in both North and South America by C. sapidus Reovirus 1 (CsRV1), a double stranded RNA virus. The 12 genome segments of a North American strain of CsRV1 were sequenced using Ion Torrent technology. Putative functions could be assigned for 3 of the 13 proteins encoded in the genome, based on their similarity to proteins encoded in other reovirus genomes. Comparison of the CsRV1 RNA-dependent RNA polymerase (RdRP) sequence to genomes of other crab-infecting reoviruses shows that it is similar to the mud crab reovirus found in Scylla serrata and WX-2012 in Eriocheir sinensis, Chinese mitten crab, and supports the idea that there is a distinct "Crabreo" genus, different from Seadornavirus and Cardoreovirus, the two closest genera in the Reoviridae. A region of 98% nucleotide sequence identity between CsRV1 and the only available sequence of the P virus of Macropipus depurator suggests that these two viruses may be closely related. An 860 nucleotide region of the CsRV1 RdRP gene was amplified and sequenced from 15 infected crabs collected from across the geographic range of C. sapidus. Pairwise analysis of predicted protein sequences shows that CsRV1 strains in Brazil can be distinguished from those in North America based on conserved residues in this gene. The sequencing, annotation, and preliminary population metrics of the genome of CsRV1 should facilitate additional studies in diverse disciplines, including structure-function relationships of reovirus proteins, investigations into the evolution of the Reoviridae, and biogeographic research on the connectivity of C. sapidus populations across the Northern and Southern hemispheres.