The Role of IL-27 in Susceptibility to Post-Influenza Staphylococcus Aureus Pneumonia

Influenza is a common respiratory virus and Staphylococcus aureus frequently causes secondary pneumonia during influenza infection, leading to increased morbidity and mortality. Influenza has been found to attenuate subsequent Type 17 immunity, enhancing susceptibility to secondary bacterial infections. IL-27 is known to inhibit Type 17 immunity, suggesting a potential critical role for IL-27 in viral and bacterial co-infection

Limits to Rest-Frame Ultraviolet Emission From Far-Infrared-Luminous z~6 Quasar Hosts

We report on a Hubble Space Telescope search for rest-frame ultraviolet emission from the host galaxies of five far-infrared-luminous $z\simeq{}6$ quasars and the $z=5.85$ hot-dust free quasar SDSS J0005-0006. We perform 2D surface brightness modeling for each quasar using a Markov-Chain Monte-Carlo estimator, to simultaneously fit and subtract the quasar point source in order to constrain the underlying host galaxy emission. We measure upper limits for the quasar host galaxies of $m_J>22.7$ mag and $m_H>22.4$ mag, corresponding to stellar masses of $M_\ast<2\times10^{11}M_\odot$. These stellar mass limits are consistent with the local $M_{\textrm{BH}}$-$M_\ast$ relation. Our flux limits are consistent with those predicted for the UV stellar populations of $z\simeq6$ host galaxies, but likely in the presence of significant dust ($\langle A_{\mathrm{UV}}\rangle\simeq 2.6$ mag). We also detect a total of up to 9 potential $z\simeq6$ quasar companion galaxies surrounding five of the six quasars, separated from the quasars by 1.4''-3.2'', or 8.4-19.4 kpc, which may be interacting with the quasar hosts. These nearby companion galaxies have UV absolute magnitudes of -22.1 to -19.9 mag, and UV spectral slopes $\beta$ of -2.0 to -0.2, consistent with luminous star-forming galaxies at $z\simeq6$. These results suggest that the quasars are in dense environments typical of luminous $z\simeq6$ galaxies. However, we cannot rule out the possibility that some of these companions are foreground interlopers. Infrared observations with the James Webb Space Telescope will be needed to detect the $z\simeq6$ quasar host galaxies and better constrain their stellar mass and dust content.Comment: 22 pages, 13 figures. Accepted for publication in Ap

STAT2 Signaling Regulates Macrophage Phenotype During Influenza and Bacterial Super-Infection

Influenza is a common respiratory virus that infects between 5 and 20% of the US population and results in 30,000 deaths annually. A primary cause of influenza-associated death is secondary bacterial pneumonia. We have previously shown that influenza induces type I interferon (IFN)-mediated inhibition of Type 17 immune responses, resulting in exacerbation of bacterial burden during influenza and Staphylococcus aureus super-infection. In this study, we investigated the role of STAT2 signaling during influenza and influenza-bacterial super-infection in mice. Influenza-infected STAT2−/− mice had increased morbidity, viral burden, and inflammation when compared to wild-type mice. Despite an exaggerated inflammatory response to influenza infection, we found increased bacterial control and survival in STAT2 deficient mice during influenza-MRSA super-infection compared to controls. Further, we found that increased bacterial clearance during influenza-MRSA super-infection is not due to rescue of Type 17 immunity. Absence of STAT2 was associated with increased accumulation of M1, M2 and M1/M2 co-expressing macrophages during influenza-bacterial super-infection. Neutralization of IFNγ (M1) and/or Arginase 1 (M2) impaired bacterial clearance in Stat2−/− mice during super-infection, demonstrating that pulmonary macrophages expressing a mixed M1/M2 phenotype promote bacterial control during influenza-bacterial super-infection. Together, these results suggest that the STAT2 signaling is involved in suppressing macrophage activation and bacterial control during influenza-bacterial super-infection. Further, these studies reveal novel mechanistic insight into the roles of macrophage subpopulations in pulmonary host defense

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Nonrandom selection and multiple blood feeding of human hosts by Anopheles vectors: implications for malaria transmission in Papua New Guinea

Nonrandom selection and multiple blood feeding of human hosts by Anopheles mosquitoes may exacerbate malaria transmission. Both patterns of blood feeding and their relationship to malaria epidemiology were investigated in Anopheles vectors in Papua New Guinea (PNG). Blood samples from humans and mosquito blood meals were collected in villages and human genetic profiles (“fingerprints”) were analyzed by genotyping 23 microsatellites and a sex-specific marker. Frequency of blood meals acquired from different humans, identified by unique genetic profiles, was fitted to Poisson and negative binomial distributions to test for nonrandom patterns of host selection. Blood meals with more than one genetic profiles were classified as mosquitoes that fed on multiple humans. The age of a person bitten by a mosquito was determined by matching the blood-meal genetic profile to the villagers’ genetic profiles. Malaria infection in humans was determined by PCR test of blood samples. The results show nonrandom distribution of blood feeding among humans, with biased selection toward males and individuals aged 15–30 years. Prevalence of Plasmodium falciparum infection was higher in this age group, suggesting males in this age range could be super-spreaders of malaria parasites. The proportion of mosquitoes that fed on multiple humans ranged from 6% to 13% among villages. The patterns of host utilization observed here can amplify transmission and contribute to the persistence of malaria in PNG despite efforts to suppress it with insecticidal bed nets. Excessive feeding on males aged 15–30 years underscores the importance of targeted interventions focusing on this demographic group