Immunology of Infectious Disease News Volume 3.26 | Jul 15 2015

Innate Immune Defenses Mediated by Two ILC Subsets Are Critical for Protection against Acute Clostridium difficile Infection
To identify immune pathways that mediate recovery from C. difficile infection, scientists challenged C57BL/6, Rag1^−/− (which lack T and B cells), and Rag2^−/− Il2rg^−/− mice (which additionally lack innate lymphoid cells [ILCs]) with C. difficile. [Cell Host Microbe] Abstract | Graphical Abstract

Long Noncoding RNA Derived from CD244 Signaling Epigenetically Controls CD8⁺ T-Cell Immune Responses in Tuberculosis Infection
Investigators showed that active human tuberculosis infection up-regulates CD244 and CD244 signaling-associated molecules in CD8⁺ T cells and that blockade of CD244 signaling enhances production of IFN-γ and TNF-α. [Proc Natl Acad Sci USA] Abstract

IFNγ and IL-12 Restrict Th2 Responses during Helminth/Plasmodium Co-Infection and Promote IFNγ from Th2 Cells
Researchers observed reduced anti-helminth Th2 cell responses and compromised anti-helminth immunity during Heligmosomoides polygyrus and Plasmodium chabaudi co-infection. [PLoS Pathog] Full Article

Circulating Human CD27⁻IgA⁺ Memory B Cells Recognize Bacteria with Polyreactive Igs
The vast majority of IgA production occurs in mucosal tissue following T cell–dependent and T cell–independent Ag responses. To study the nature of each of these responses, investigators analyzed the gene-expression and Ig-reactivity profiles of T cell–dependent CD27⁺IgA⁺ and T cell–independent CD27⁻IgA⁺ circulating memory B cells. [J Immunol] Abstract

Litomosoides Sigmodontis Induces TGF-β Receptor Responsive, IL-10-Producing T Cells that Suppress Bystander T-Cell Proliferation in Mice
Helminth parasites suppress immune responses to prolong their survival within the mammalian host. Thereby not only helminth-specific but also non-helminth-specific bystander immune responses are suppressed. Investigators use the murine model of Litomosoides sigmodontis infection to elucidate the underlying mechanisms leading to this bystander T-cell suppression. [Eur J Immunol] Abstract

HIV

The Tat Inhibitor Didehydro-Cortistatin A Prevents HIV-1 Reactivation from Latency
Scientists showed that the Tat inhibitor didehydro-cortistatin A, unlike other antiretrovirals, reduces residual levels of viral transcription in several models of HIV latency, breaks the Tat-mediated transcriptional feedback loop, and establishes a nearly permanent state of latency, which greatly diminishes the capacity for virus reactivation. [mBio] Full Article | Press Release

Loss of Marginal Zone B-Cells in SHIV_SF162P4 Challenged Rhesus Macaques Despite Control of Viremia to Low or Undetectable Levels in Chronic Infection
Investigators characterized rhesus macaque marginal zone (MZ) B cells, present in secondary lymphoid tissue but not peripheral blood, as CD19⁺, CD20⁺, CD21^hi, IgM⁺, CD22⁺, CD38⁺, BTLA⁺, CD40⁺, CCR6⁺ and BCL-2⁺. Compared to healthy macaques, SHIV_SF162P4-infected animals showed decreased total B cells and MZ B cells and increased MZ B cell Ki-67 expression early in chronic infection. [Virology] Abstract

Immunologic and Virologic Progression in HIV Controllers: The Role of Viral “Blips” and Immune Activation in the ANRS CO21 CODEX Study
Researchers investigated the rate of immunologic and/or virologic progression and its determinants in the ANRS CO21/CODEX cohort. Immunologic progression was defined as a lasting fall in CD4⁺ T cell count below 350/mm³ or more than 200/mm³ with a baseline count below 600/mm³. [PLoS One] Full Article

Discovery of Genetic Variants of the Kinases that Activate Tenofovir in a Compartment-Specific Manner
Tenofovir (TFV) is used in combination with other antiretroviral drugs for human immunodeficiency virus treatment and prevention. Peripheral blood mononuclear cells, vaginal, and colorectal tissues were transfected with siRNA targeting nucleotide kinases, incubated with TFV, and TFV-monophosphate and TFV-diphosphate were measured using mass spectrometry–liquid chromatography. [EBioMedicine] Full Article | Press Release

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UTHealth Researcher Awarded $1.9 Million Grant to Study C. diff Infections
Charles Darkoh, Ph.D., a researcher at The University of Texas Health Science Center at Houston (UTHealth) School of Public Health, was recently awarded a five-year, $1.9 million R01 grant by The National Institutes of Health to develop a non-antibiotic treatment for Clostridium difficile infections. [The University of Texas Health Science Center at Houston] Press Release

Vanderbilt University Medical Center Joins Human Vaccines Project as First Scientific Hub
Vanderbilt University Medical Center (VUMC), the Human Vaccines Project and the International AIDS Vaccine Initiative are pleased to announce that VUMC has become the Project’s first scientific hub. [International AIDS Vaccine Initiative] Press Release

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