The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication.

Severity of COVID-19 is affected by multiple factors; however, it is not understood how the inflammatory milieu of the lung at the time of SARS-CoV-2 exposure affects the control of viral replication. Here, we demonstrate that immune events in the mouse lung closely preceding SARS-CoV-2 infection affect viral control and identify innate immune pathways that limit viral replication. Pulmonary inflammatory stimuli including resolved, antecedent respiratory infections with or influenza, ongoing pulmonary infection, ovalbumin/alum-induced asthma, or airway administration of TLR ligands and recombinant cytokines all establish an antiviral state in the lung that restricts SARS-CoV-2 replication.

A Small Intestinal Helminth Infection Alters Colonic Mucus and Shapes the Colonic Mucus Microbiome.

Infecting humans with controlled doses of small intestinal helminths, such as human hookworm, is proposed as a therapy for the colonic inflammatory disease ulcerative colitis. Strengthening the colonic mucus barrier is a potential mechanism by which small intestinal helminths could treat ulcerative colitis. In this study, we compare C57BL/6 mice infected with the small intestinal helminth and uninfected controls to investigate changes in colonic mucus.

The third generation AKR1C3-activated prodrug, ACHM-025, eradicates disease in preclinical models of aggressive T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy that expresses high levels of the enzyme aldo-keto reductase family 1 member C3 (AKR1C3). To exploit this finding, we developed a novel prodrug, ACHM-025, which is selectively activated by AKR1C3 to a nitrogen mustard DNA alkylating agent. We show that ACHM-025 has potent in vivo efficacy against T-ALL patient-derived xenografts (PDXs) and eradicated the disease in 7 PDXs.

The SARS-CoV-2 neutralising antibody profile of New Zealand adults in 2023: Impact of vaccination and infection.

The successive dominance of SARS-CoV-2 omicron sublineages presents challenges for vaccination strategies with respect to the antigenic content of boosters. New Zealand's COVID-19 elimination strategy (2020-2021) ensured the major vaccination campaign (Pfizer-BioNTech BNT162b2) was completed pre-omicron in an infection-naive population, providing a unique setting to explore the impact of omicron infection waves on vaccine responses. This study compared neutralising antibodies (NAb) to eight SARS-CoV-2 omicron sublineages 28-days and 11-months after a third dose.

Mitochondrial DNA damage, repair, and replacement in cancer.

Mitochondria are vital organelles with their own DNA (mtDNA). mtDNA is circular and composed of heavy and light chains that are structurally more accessible than nuclear DNA (nDNA). While nDNA is typically diploid, the number of mtDNA copies per cell is higher and varies considerably during development and between tissues.

Controlled infection with cryopreserved human hookworm induces CTLA-4 expression on Tregs and upregulates tryptophan metabolism.

Infecting humans with controlled doses of helminths, such as human hookworm (termed hookworm therapy), is proposed to prevent or treat various intestinal and extraintestinal diseases. However, full-scale clinical trials examining hookworm therapy are limited by the inability to scale-up the production of hookworm larvae to infect sufficient numbers of patients. With the aim of overcoming this challenge, this study infected four healthy individuals with hookworm larvae that had been reanimated from cryopreserved eggs to examine their viability and immunogenicity.

The immunoregulatory potential of eosinophil subsets.

Eosinophils have traditionally been viewed as pathological effector cells primarily involved in antiparasitic and allergic immune reactions; however, it is becoming increasingly apparent that eosinophils are multifaceted leukocytes that contribute to a variety of roles in both health and disease. Recent research shows that eosinophils play important immunoregulatory roles across various tissue sites including the gastrointestinal tract, adipose tissue, lung, liver, heart, muscles, thymus and bone marrow. With recent advances in our knowledge and appreciation of eosinophil immunoregulatory functions at these tissue sites, as well as emerging research demonstrating the existence of distinct subsets of eosinophils, a review of this topic is timely.

Nourishing the Infant Gut Microbiome to Support Immune Health: Protocol of SUN (Seeding Through Feeding) Randomized Controlled Trial.

Background: The introduction of complementary foods during the first year of life influences the diversity of the gut microbiome. How this diversity affects immune development and health is unclear.

Objective: This study evaluates the effect of consuming kūmara or kūmara with added banana powder (resistant starch) compared to a reference control at 4 months post randomization on the prevalence of respiratory tract infections and the development of the gut microbiome.

Helminth infection driven gastrointestinal hypermotility is independent of eosinophils and mediated by alterations in smooth muscle instead of enteric neurons.

Intestinal helminth infection triggers a type 2 immune response that promotes a 'weep-and sweep' response characterised by increased mucus secretion and intestinal hypermotility, which function to dislodge the worm from its intestinal habitat. Recent studies have discovered that several other pathogens cause intestinal dysmotility through major alterations to the immune and enteric nervous systems (ENS), and their interactions, within the gastrointestinal tract. However, the involvement of these systems has not been investigated for helminth infections.

Reinterpretation of prostate cancer pathology by Appl1, Sortilin and Syndecan-1 biomarkers.

The diagnosis of prostate cancer using histopathology is reliant on the accurate interpretation of prostate tissue sections. Current standards rely on the assessment of Haematoxylin and Eosin (H&E) staining, which can be difficult to interpret and introduce inter-observer variability. Here, we present a digital pathology atlas and online resource of prostate cancer tissue micrographs for both H&E and the reinterpretation of samples using a novel set of three biomarkers as an interactive tool, where clinicians and scientists can explore high resolution histopathology from various case studies.

Best practices for user consultation in flow cytometry shared resource laboratories.

This "Best Practices in User Consultation" article is the result of a 2022 International Society for the Advancement of Cytometry (ISAC) membership survey that collected valuable insights from the shared research laboratory (SRL) community and of a group discussion at the CYTO 2022 workshop of the same name. One key takeaway is the importance of initiating a consultation at the outset of a flow cytometry project, particularly for trainees. This approach enables the improvement and standardization of every step, from planning experiments to interpreting data.

Tuning CAR T-cell therapies for efficacy and reduced toxicity.

Chimeric antigen receptor (CAR) T-cell therapies are a standard of care for certain relapsed or refractory B-cell cancers. However, many patients do not respond to CAR T-cell therapy or relapse later, short- and long-term toxicities are common, and current CAR T-cell therapies have limited efficacy for solid cancers. The gene engineering inherent in CAR T-cell manufacture offers an unprecedented opportunity to control cellular characteristics and design products that may overcome these limitations.

Venetoclax-obinutuzumab for previously untreated chronic lymphocytic leukemia: 6-year results of the randomized phase 3 CLL14 study.

In the CLL14 study, patients with previously untreated chronic lymphocytic leukemia (CLL) and coexisting conditions were randomized to 12 cycles of venetoclax-obinutuzumab (Ven-Obi, n = 216) or chlorambucil-obinutuzumab (Clb-Obi, n = 216). Progression-free survival (PFS) was the primary end point. Key secondary end points included time-to-next-treatment (TTNT), rates of undetectable minimal residual disease (uMRD), overall survival (OS), and rates of adverse events.

Highlight of 2023: Advances in germinal centers.

In this article for the Highlight of 2023 series, we discuss recent advances in the fundamental biology of the germinal center response. These discoveries provide important insights as to how the germinal center contributes to protection against infection, and also highlights opportunities for future vaccine development.

Helminth infection induces a distinct subset of CD101 lung tissue-infiltrating eosinophils that are differentially regulated by type 2 cytokines.

Eosinophils play divergent roles in health and disease, contributing to both immunoregulatory and proinflammatory responses. Helminth infection is strongly associated with eosinophilia and the induction of the type 2 cytokines interleukin (IL)-5, IL-4 and IL-13. This study aimed to elucidate the heterogeneity of pulmonary eosinophils in response to helminth infection and the roles of IL-5, IL-4 and IL-13 in driving pulmonary eosinophil responses.

Tonic type 2 immunity is a critical tissue checkpoint controlling autoimmunity in the skin.

Immunoregulatory mechanisms established in the lymphoid organs are vital for preventing autoimmunity. However, the presence of similar mechanisms in non-lymphoid tissues remains unclear. Through transcriptomic and lipidomic analyses, we find a negative association between psoriasis and fatty acid metabolism, as well as Th2 signature.

Nalfurafine promotes myelination in vitro and facilitates recovery from cuprizone + rapamycin-induced demyelination in mice.

The kappa opioid receptor has been identified as a promising therapeutic target for promoting remyelination. In the current study, we evaluated the ability of nalfurafine to promote oligodendrocyte progenitor cell (OPC) differentiation and myelination in vitro, and its efficacy in an extended, cuprizone-induced demyelination model. Primary mouse (C57BL/6J) OPC-containing cultures were treated with nalfurafine (0.

Marginal zone lymphomas: a consensus practice statement from the Australasian Lymphoma Alliance.

Marginal zone lymphomas (MZLs) are a rare, indolent group of non-Hodgkin lymphomas with different diagnostic, genetic and clinical features and therapeutic implications. The most common is extranodal MZL of mucosa-associated lymphoid tissue, followed by splenic MZL and nodal MZL. Patients with MZL generally have good outcomes with long survival rates but frequently have a relapsing/remitting course requiring several lines of therapy.

Cell shape sensing licenses dendritic cells for homeostatic migration to lymph nodes.

Immune cells experience large cell shape changes during environmental patrolling because of the physical constraints that they encounter while migrating through tissues. These cells can adapt to such deformation events using dedicated shape-sensing pathways. However, how shape sensing affects immune cell function is mostly unknown.

A Glycolipid-Peptide-Hapten Tricomponent Conjugate Vaccine Generates Durable Antihapten Antibody Responses in Mice.

Eliciting an antihapten antibody response to vaccination typically requires the use of constructs where multiple copies of the hapten are covalently attached to a larger carrier molecule. The carrier is required to elicit T cell help via presentation of peptide epitopes on major histocompatibility complex (MHC) class II molecules; as such, attachment to full-sized proteins, alone or in a complex, is generally used to account for the significant MHC diversity in humans. While such carrier-based vaccines have proven extremely successful, particularly in protecting against bacterial diseases, they can be challenging to manufacture, and repeated use can be compromised by pre-existing immunity against the carrier.

Residual OXPHOS is required to drive primary and metastatic lung tumours in an orthotopic breast cancer model.

Background: Fast adaptation of glycolytic and mitochondrial energy pathways to changes in the tumour microenvironment is a hallmark of cancer. Purely glycolytic ρ tumour cells do not form primary tumours unless they acquire healthy mitochondria from their micro-environment. Here we explored the effects of severely compromised respiration on the metastatic capability of 4T1 mouse breast cancer cells.