Volume 4.10 | Mar 16

Immunology of Infectious Disease News 4.10 March 16, 2016
Immunology of Infectious Disease News
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Interleukin-27-Producing CD4+ T Cells Regulate Protective Immunity during Malaria Parasite Infection
Scientists described regulatory CD4+ T cells that produce interleukin-27 (IL-27) in response to T cell receptor stimulation during malaria infection, inhibiting IL-2 production and clonal expansion of other T cells in an IL-27-dependent manner. [Immunity] Abstract | Graphical Abstract
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PUBLICATIONS (Ranked by impact factor of the journal)
Type I Interferon Signaling Prevents IL-1β-Driven Lethal Systemic Hyperinflammation during Invasive Bacterial Infection of Soft Tissue
Investigators report that type I interferon signaling protects the host against invasive Streptococcus pyogenes infection by restricting inflammation-driven damage in distant tissues. [Cell Host Microbe]
Abstract | Graphical Abstract

Therapeutic and Prophylactic Activity of Itraconazole against Human Rhinovirus Infection in a Murine Model
Researchers investigated whether itraconazole (ICZ) can protect cells from human rhinovirus (HRV)-induced cytotoxicity. The numbers of immune cells, including granulocytes and monocytes, were reduced in bronchoalveolar lavage fluid (BALF) by ICZ administration after HRV1B infection, corresponding to decreased pro-inflammatory cytokine and chemokine levels in BALF. [Sci Rep] Full Article

Experimental Persistent Infection of BALB/c Mice with Small-Colony Variants of Burkholderia pseudomallei Leads to Concurrent Upregulation of PD-1 on T Cells and Skewed Th1 and Th17 Responses
B. pseudomallei appeared to upregulate the expression of PD-1 on T cells to evade host immune responses, which likely facilitates bacterial persistence in the host. [PLoS Negl Trop Dis] Full Article

RSV Pulmonary Infection in Humanized Mice Induces Human Anti-RSV Immune Responses and Pathology
Scientists assessed respiratory syncytial virus (RSV)-specific human innate, humoral and cellular immune responses in humanized mice with functional human CD4+ T and B cells that were generated by introduction of HLA class II genes, various human cytokines and human B cell activation factor by adeno-associated vector, followed by engraftment of human hematopoietic stem cells to immunodeficient NOD scid gamma mice. [J Virol] Abstract

Circulating T Follicular Helper Cells Are Associated with Rapid Virological Response in Chronic Hepatitis C Patients Undergoing Peginterferon Therapy
Researchers investigated the role of circulating CXCR5+ CD4+ T follicular helper cells, CD19+ B cells and the associated cytokines in patients with chronic hepatitis C virus infection. [Int Immunopharmacol] Abstract


Altered Virome and Bacterial Microbiome in Human Immunodeficiency Virus-Associated Acquired Immunodeficiency Syndrome
Researchers characterized the enteric virome and bacterial microbiome in a cohort of Ugandan patients, including HIV-uninfected or HIV-infected subjects and those either treated with anti-retroviral therapy (ART) or untreated. Low peripheral CD4 T cell counts were associated with an expansion of enteric adenovirus sequences and this increase was independent of ART treatment. [Cell Host Microbe]
Abstract | Graphical Abstract | Press Release

SIV Infection-Mediated Changes in Gastrointestinal Bacterial Microbiome and Virome Are Associated with Immunodeficiency and Prevented by Vaccination
Investigators performed a longitudinal study of a vaccine cohort to define the natural history of changes in the fecal metagenome in simian immunodeficiency virus (SIV)-infected monkeys. Matched rhesus macaques were either uninfected or intrarectally challenged with SIV, with a subset receiving the Ad26 vaccine, an adenovirus vector expressing the viral Env/Gag/Pol antigens. [Cell Host Microbe] Abstract | Graphical Abstract

Lower Viral Loads and Slower CD4 Decline in MRKAd5 HIV-1 Vaccinees Expressing Disease-Susceptible HLA-B*58:02
The authors investigated the HLA-specific impact of the MRKAd5 HIV-1 Gag/Pol/Nef vaccine in a subset of the infected Phambili cohort in whom the disease-susceptible HLA-B*58:02 is highly prevalent. [J Infect Dis] Abstract | Full Article

Expansion of Myeloid-Derived Suppressor Cells Promotes Differentiation of Regulatory T Cells in HIV-1+ Individuals
Researchers provide evidence that HIV-induced expansion of monocytic myeloid-derived suppressor cells (M-MDSCs) promote the differentiation of Foxp3+ regulatory T cells. They observed a dramatic increase in M-MDSC frequencies in the peripheral blood of HIV-1 seropositive (HIV-1+) individuals, even in those on antiretroviral therapy with undetectable viremia, when compared to healthy subjects. [AIDS] Abstract

Antibodies Elicited by Multiple Envelope Glycoprotein Immunogens in Primates Neutralize Primary Human Immunodeficiency Viruses (HIV-1) Sensitized by CD4-Mimetic Compounds
Investigators showed that CD4-mimetic compounds sensitize primary HIV-1 to neutralization by antibodies that can be elicited in monkeys and humans within six months by several envelope glycoproteins vaccine candidates, including gp120 monomers. [J Virol] Abstract

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Pediatric HIV Infection: The Potential for Cure
The authors describe the influence of early initiation of antiretroviral therapy, of immune ontogeny and of maternal factors on the potential for HIV cure in children and discusses the unique immunotherapeutic opportunities and obstacles that pediatric infection may present. [Nat Rev Immunol] Abstract

Dissecting How CD4 T Cells Are Lost During HIV Infection
Although the replicative life cycle of HIV within CD4 T cells is understood in molecular detail, less is known about how this human retrovirus promotes the loss of CD4 T lymphocytes. Recent studies have highlighted how abortive infection of resting and thus nonpermissive CD4 T cells in lymphoid tissues triggers a lethal innate immune response against the incomplete DNA products generated by inefficient viral reverse transcription in these cells. [Cell Host Microbe] Abstract

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Extension of TEACH Study Based on Supportive First Study Results
MOLOGEN AG announced that the TEACH study with its immunomodulatory lefitolimod in HIV patients will be extended as a result of the broad immune system activation induced by the drug. [Press release from MOLAGEN AG discussing research to be presented at the Keystone Symposia Conference on HIV Vaccines, Olympic Valley] Press Release

Antioxidants Improve Lung Immune Markers in HIV-Infected Patients Who Are Immune Non-Responders
Dietary supplementation with zinc and S-adenosylmethionine, an antioxidant, can improve the function of immune cells in the lungs, a small study involving 14 HIV-infected patients indicated. [Press release from Emory University discussing research presented at the 23rd Conference on Retroviruses and Opportunistic Infections (CROI), Boston] Press Release

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NIAID to Fund Further Study of Dapivirine Vaginal Ring for HIV Prevention
The National Institute of Allergy and Infectious Diseases (NIAID) announced that it would move forward with an open-label extension study of an HIV prevention tool for women: a silicone ring that continuously releases the experimental antiretroviral drug dapivirine in the vagina. [National Institute of Allergy and Infectious Diseases] Press Release

Benitec’s Hepatitis B Therapy Reduces HBV DNA by 98.5% In Vivo
Benitec Biopharma Limited announced that BB-HB-331, a DNA-directed RNA interference therapy targeting the hepatitis B virus (HBV), demonstrates robust and durable suppression of HBV in vivo following a single administration. [Benitec Biopharma Limited] Press Release
NHS England Launches National Program to Combat Antibiotic Overusage
NHS England launched the world’s largest healthcare incentive scheme for hospitals, family doctors and other health service providers to prevent the growing problem of antibiotic resistance. [NHS England] Editorial

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Therapeutic Goods Administration (Australia)
NEW Banff Conference on Infectious Diseases 2016
June 1-4, 2016
Banff, Canada

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NEW Postdoctoral Position – Dendritic Cells in Inflammation and Infection (Centre d’Immunologie de Marseille Luminy)

NEW Postdoctoral Position – Innate Immunity (Fred Hutchinson Cancer Research Center)

Senior Scientist – Immunology and Cell Separation (STEMCELL Technologies Inc.)

Postdoctoral Fellow – Immunology (Ragon Institute of MGH, MIT and Harvard)

Postdoctoral Fellow – Immune Responses to Vaccines (Boston Children’s Hospital)

Principal Scientist – Infectious Disease (Janssen Pharmaceutica N.V.)

Postdoctoral Fellow – Drug Delivery for HIV (Northwestern University)

Principal Investigators – Infectious Diseases (CCID)

Administrative Head – Vaccine and Infectious Disease (Fred Hutchinson Cancer Research Center)

Global Medical Leader – Infectious Diseases (F. Hoffmann-La Roche)

Research Technician I – HIV Vaccine Trials (Fred Hutchinson Cancer Research Center)

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