Immunology of Infectious Disease News Volume 1.12 | Jun 5 2013

PUBLICATIONS (Ranked by impact factor of the journal)

The Human Malaria Parasite Pfs47 Gene Mediates Evasion of the Mosquito Immune System
A combination of genetic mapping, linkage group selection, and functional genomics was used to identify Pfs47 as a Plasmodium falciparum gene that allows the parasite to infect Anopheles gambiae  without activating the mosquito immune system. Disruption of Pfs47 greatly reduced parasite survival in the mosquito, and this phenotype could be reverted by genetic complementation of the parasite or by disruption of the mosquito complement-like system. [Science] Abstract

Antibody to a Conserved Antigenic Target Is Protective against Diverse Prokaryotic and Eukaryotic Pathogens
Investigators report that many microbial pathogens lacking an identifiable intercellular adhesion or polyglucosamine locus produce ß-(1→6)-linked poly-N-acetyl-d-glucosamine (PNAG), including Gram-positive, Gram-negative, and fungal pathogens, as well as protozoa, e.g., Trichomonas vaginalis, Plasmodium berghei, and sporozoites and blood-stage forms of Plasmodium falciparum. Natural antibody to PNAG is common in humans and animals and binds primarily to the highly acetylated glycoform of PNAG but is not protective against infection due to lack of deposition of complement opsonins.
[Proc Natl Acad Sci USA] Abstract | Press Release

Intranasal Antibody Gene Transfer in Mice and Ferrets Elicits Broad Protection Against Pandemic Influenza
Advances in human antibody isolation have led to the discovery of monoclonal antibodies that have broad neutralizing activity against various influenza strains, although their direct use for prophylaxis is impractical. To overcome this limitation, the authors delivered antibody via adeno-associated virus vectors to the site of initial infection, which, for respiratory viruses such as influenza, is the nasopharyngeal mucosa. [Sci Transl Med] Abstract | Press Release

Enhanced T Cell Function in a Mouse Model of Human Glycosylation
Researchers found that, upon lymphocytic choriomeningitis virus infection, CMP-N-acetylneuraminic acid hydroxylase^-/- mice make more lymphocytic choriomeningitis virus-specific T cells than wild-type mice, and these T cells are more polyfunctional. Therefore, a uniquely human glycosylation mutation, modeled in mice, leads to a more proliferative and active T cell population. [J Immunol] Abstract

Toll-Like Receptor 2-Independent Host Innate Immune Response against an Epidemic Strain of Streptococcus suis that Causes a Toxic Shock-Like Syndrome in Humans
The in vivo role of Toll-like receptor 2 (TLR2) in systemic infections caused by S. suis sequence type (ST)1 or ST7 strains using TLR2 deficient (TLR2^−/−) mice was evaluated. TLR2-mediated recognition significantly contributes to the acute disease caused by the highly virulent S. suis ST1 strain, since the TLR2^−/− mice remained unaffected when compared to wild type mice. [PLoS One] Full Article

HIV

Human Plasmacytoid Dendritic Cells Efficiently Capture HIV-1 Envelope Glycoproteins via CD4 for Antigen Presentation
Advances in HIV-1 vaccine clinical trials and preclinical research indicate that the virus envelope glycoproteins (Env) are likely to be an essential component of a prophylactic vaccine. Efficient antigen uptake and presentation by dendritic cells (DCs) is important for strong CD4⁺ Th cell responses and the development of effective humoral immune responses. The authors examined the capacity of distinct primary human DC subsets to internalize and present recombinant Env to CD4⁺ T cells. [J Immunol] Abstract

TLR2 Activated B Cells Are Phenotypically Similar to the Abnormal Circulating B Cells Seen Preceding the Diagnosis of AIDS Related Non-Hodgkin lymphoma (NHL) Diagnosis
Investigators examined whether surface markers expressed on activated and/or germinal center B cells, and activation-induced cytidine deaminase expression, were elevated on circulating B cells preceding AIDS-NHL, as well as if Toll-like receptor (TLR) signaling contributes to this activated B cell phenotype. [JAIDS] Abstract

Low-Dose Growth Hormone for 40 Weeks Induces Human Immunodeficiency Virus-1-Specific T-Cell Responses in Patients on Effective Combination Antiretroviral Therapy
Investigators report that administration of low-dose recombinant human growth hormone over 40 weeks with effective combination antiretroviral therapy (cART) resulted in greater improvement of T-lymphocyte function than observed with cART alone, and provide further evidence that such an approach may also reduce levels of immune activation. [Clin Exp Immunol] Abstract

Viral Protein R Upregulates Expression of ULBP2 on Uninfected Bystander Cells during HIV-1 Infection of Primary CD4+ T Lymphocytes
HIV-1 viral protein R (Vpr) triggers natural killer (NK) cell-mediated lysis of infected cells by upregulating ULBP2, a ligand of the NKG2D receptor, through activation of the ATR-mediated DNA damage response.  Herein, scientists demonstrated that Vpr augments ULBP2 expression on both infected and uninfected bystander cells during HIV-1 infection of primary CD4+ T lymphocytes. [Virology] Abstract

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Inflammation in Tuberculosis: Interactions, Imbalances and Interventions
Proinflammatory cytokines, including interferons, tumor necrosis factor and interleukin 1 along with microRNAs and eicosanoids form an interactive network during tuberculosis. Cross-regulation between proinflammatory mediators strongly impacts on infected cell death patterns. These processes, in concert with local concentrations of proteases, such as cathepsins, serpins and matrix-metalloproteinases, affect tissue integrity, shape the architecture of granulomas and modulate tissue repair. [Curr Opin Immunol] Abstract

Restrictions to HIV-1 Replication in Resting CD4⁺ T Lymphocytes
The authors summarize their current molecular and pathophysiological understanding of the multi-faceted interactions of HIV-1 with resting CD4⁺ T lymphocytes. [Cell Res] Full Article

Innate Immune Detection of Microbial Nucleic Acids
Recent developments in pattern recognition receptors research have uncovered important new molecular details as to how Toll-like receptors and retinoic acid-inducible gene-I-like receptors distinguish pathogen from self RNA, while the discovery of cytosolic DNA sensing pathways for interferon induction has revealed completely new innate signaling mechanisms, and also questions how innate immunity discriminates between self and non-self DNA, if at all. [Trends Microbiol] Abstract

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National Institutes of Health to Fund Clinical Research Network on Antibacterial Resistance
Duke University, Durham, N.C., has been awarded $2 million to initiate a new clinical research network focused on antibacterial resistance. Total funding for the leadership group cooperative agreement award could reach up to $62 million through 2019. [National Institutes of Health] Press Release

GSK Strengthens Vaccines Business with Acquisition of Okairos
GlaxoSmithKline (GSK) announced that it has acquired Okairos AG (Okairos), a specialist developer of vaccine platform technologies for €250 million in cash. Swiss-based Okairos has developed a novel vaccine platform technology which is expected to play an important role in GSK’s development of new prophylactic vaccines as well as new classes of therapeutic vaccines. [GlaxoSmithKline plc] Press Release

iBio Technology Produces Vaccine Candidate for Recently Emerged H7N9 Influenza Virus
iBio, Inc. announced the production of a vaccine candidate for the newly emerged H7N9 influenza virus by an independent third party laboratory using the iBioLaunch™ platform. This validation milestone was achieved in 21 days as measured from initial antigen sequence information to purification of recombinant protein. [iBio, Inc.] Press Release

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