Tobias R. Kollmann

Bio: Tobias R. Kollmann is an academic researcher from Telethon Institute for Child Health Research. The author has contributed to research in topics: Vaccination & Immune system. The author has an hindex of 48, co-authored 181 publications receiving 7929 citations. Previous affiliations of Tobias R. Kollmann include Yeshiva University & University of Washington.

Early infancy microbial and metabolic alterations affect risk of childhood asthma

Abstract: Asthma is the most prevalent pediatric chronic disease and affects more than 300 million people worldwide. Recent evidence in mice has identified a "critical window" early in life where gut microbial changes (dysbiosis) are most influential in experimental asthma. However, current research has yet to establish whether these changes precede or are involved in human asthma. We compared the gut microbiota of 319 subjects enrolled in the Canadian Healthy Infant Longitudinal Development (CHILD) Study, and show that infants at risk of asthma exhibited transient gut microbial dysbiosis during the first 100 days of life. The relative abundance of the bacterial genera Lachnospira, Veillonella, Faecalibacterium, and Rothia was significantly decreased in children at risk of asthma. This reduction in bacterial taxa was accompanied by reduced levels of fecal acetate and dysregulation of enterohepatic metabolites. Inoculation of germ-free mice with these four bacterial taxa ameliorated airway inflammation in their adult progeny, demonstrating a causal role of these bacterial taxa in averting asthma development. These results enhance the potential for future microbe-based diagnostics and therapies, potentially in the form of probiotics, to prevent the development of asthma and other related allergic diseases in children.

Neonatal Innate TLR-Mediated Responses Are Distinct from Those of Adults

Abstract: The human neonate and infant are unduly susceptible to infection with a wide variety of microbes. This susceptibility is thought to reflect differences from adults in innate and adaptive immunity, but the nature of these differences is incompletely characterized. The innate immune response directs the subsequent adaptive immune response after integrating information from TLRs and other environmental sensors. We set out to provide a comprehensive analysis defining differences in response to TLR ligation between human neonates and adults. In response to most TLR ligands, neonatal innate immune cells, including monocytes and conventional and plasmacytoid dendritic cells produced less IL-12p70 and IFN-α (and consequently induced less IFN-γ), moderately less TNF-α, but as much or even more IL-1β, IL-6, IL-23, and IL-10 than adult cells. At the single-cell level, neonatal innate cells generally were less capable of producing multiple cytokines simultaneously, i.e., were less polyfunctional. Overall, our data suggest a robust if not enhanced capacity of the neonate vs the adult white-blood cell TLR-mediated response to support Th17- and Th2-type immunity, which promotes defense against extracellular pathogens, but a reduced capacity to support Th1-type responses, which promote defense against intracellular pathogens.

MIFlowCyt: the minimum information about a Flow Cytometry Experiment.

Abstract: A fundamental tenet of scientific research is that published results are open to independent validation and refutation. Minimum data standards aid data providers, users, and publishers by providing a specification of what is required to unambiguously interpret experimental findings. Here, we present the Minimum Information about a Flow Cytometry Experiment (MIFlowCyt) standard, stating the minimum information required to report flow cytometry (FCM) experiments. We brought together a cross-disciplinary international collaborative group of bioinformaticians, computational statisticians, software developers, instrument manufacturers, and clinical and basic research scientists to develop the standard. The standard was subsequently vetted by the International Society for Advancement of Cytometry (ISAC) Data Standards Task Force, Standards Committee, membership, and Council. The MIFlowCyt standard includes recommendations about descriptions of the specimens and reagents included in the FCM experiment, the configuration of the instrument used to perform the assays, and the data processing approaches used to interpret the primary output data. MIFlowCyt has been adopted as a standard by ISAC, representing the FCM scientific community including scientists as well as software and hardware manufacturers. Adoptionof MIFlowCyt by the scientific and publishing communities will facilitate third-party understanding and reuse of FCM data.

Immunological mechanisms of vaccine-induced protection against COVID-19 in humans.

Abstract: Most COVID-19 vaccines are designed to elicit immune responses, ideally neutralizing antibodies (NAbs), against the SARS-CoV-2 spike protein. Several vaccines, including mRNA, adenoviral-vectored, protein subunit and whole-cell inactivated virus vaccines, have now reported efficacy in phase III trials and have received emergency approval in many countries. The two mRNA vaccines approved to date show efficacy even after only one dose, when non-NAbs and moderate T helper 1 cell responses are detectable, but almost no NAbs. After a single dose, the adenovirus vaccines elicit polyfunctional antibodies that are capable of mediating virus neutralization and of driving other antibody-dependent effector functions, as well as potent T cell responses. These data suggest that protection may require low levels of NAbs and might involve other immune effector mechanisms including non-NAbs, T cells and innate immune mechanisms. Identifying the mechanisms of protection as well as correlates of protection is crucially important to inform further vaccine development and guide the use of licensed COVID-19 vaccines worldwide.

Toll-like receptor signalling

Abstract: One of the mechanisms by which the innate immune system senses the invasion of pathogenic microorganisms is through the Toll-like receptors (TLRs), which recognize specific molecular patterns that are present in microbial components. Stimulation of different TLRs induces distinct patterns of gene expression, which not only leads to the activation of innate immunity but also instructs the development of antigen-specific acquired immunity. Here, we review the rapid progress that has recently improved our understanding of the molecular mechanisms that mediate TLR signalling.

The Human Intestinal Microbiome in Health and Disease

Abstract: The large majority of studies on the role of the microbiome in the pathogenesis of disease are correlative and preclinical; several have influenced clinical practice.

Regulation of Adaptive Immunity by the Innate Immune System

Abstract: Twenty years after the proposal that pattern recognition receptors detect invasion by microbial pathogens, the field of immunology has witnessed several discoveries that have elucidated receptors and signaling pathways of microbial recognition systems and how they control the generation of T and B lymphocyte-mediated immune responses. However, there are still many fundamental questions that remain poorly understood, even though sometimes the answers are assumed to be known. Here, we discuss some of these questions, including the mechanisms by which pathogen-specific innate immune recognition activates antigen-specific adaptive immune responses and the roles of different types of innate immune recognition in host defense from infection and injury.