Management of many bacterial infections is becoming increasingly difficult due to new and rapidly evolving pathogens with increased virulence and drug resistance. Promising alternatives to targeting pathogens, novel anti-infective approaches, harness the host’s own response to infection. To realize these promising alternatives, a comprehensive understanding of the complex interaction between different immune cells, and how they translate into infection outcome is required. Currently, our understanding of human infection is limited to studies performed at disease stages, when symptoms already evident. We believe that the early stages of infection, when bacterial numbers are relatively small, are critical in determining infection outcome, and offers a unique opportunity to eradicate infection. However, one of the least-understood periods in the course of infectious disease lies between the initial inoculation and the appearance of the first symptoms of disease. To bridge this gap, models of human disease dynamics are required, in order to characterize early immune responses which correlate to infection outcome. To achieve this goal, we used samples from the human challenge model, in which healthy volunteers are infected with Salmonella Typhi (S. Typhi). We performed single cell RNA-seq on Peripheral Blood Mononuclear Cells (PBMCs) samples from 6 individuals before and in different time-points after challenge. Three individuals developed typhoid disease and three did not. Then we comprehensively functionully characterized the immune subsets from all cell types, and found (1) immune subsets that are shared across all individuals and represent global response to S. Typhi infection; and (2) immune subset that exhibit inter-individual variability which was connected to infection outcome. Interestingly, some of these states were already evident before challenge, suggesting predisposition or protective effects to S. Typhi infection; other states were evident as early as 12 to 24 hours post challenge. These subsets are candidates to predict infection outcome at early stages of infection. 

Management of many bacterial infections is becoming increasingly difficult due to new and rapidly evolving pathogens with increased virulence and drug resistance. Promising alternatives to targeting pathogens, novel anti-infective approaches, harness the host’s own response to infection. To realize these promising alternatives, a comprehensive understanding of the complex interaction between different immune cells, and how they translate into infection outcome is required. Currently, our understanding of human infection is limited to studies performed at disease stages, when symptoms already evident. We believe that the early stages of infection, when bacterial numbers are relatively small, are critical in determining infection outcome, and offers a unique opportunity to eradicate infection. However, one of the least-understood periods in the course of infectious disease lies between the initial inoculation and the appearance of the first symptoms of disease. To bridge this gap, models of human disease dynamics are required, in order to characterize early immune responses which correlate to infection outcome. To achieve this goal, we used samples from the human challenge model, in which healthy volunteers are infected with _Salmonella_ Typhi _(S._ Typhi). We performed single cell RNA-seq on Peripheral Blood Mononuclear Cells (PBMCs) samples from 6 individuals before and in different time-points after challenge. Three individuals developed typhoid disease and three did not. Then we comprehensively functionully characterized the immune subsets from all cell types, and found (1) immune subsets that are shared across all individuals and represent global response to _S._ Typhi infection; and (2) immune subset that exhibit inter-individual variability which was connected to infection outcome. Interestingly, some of these states were already evident before challenge, suggesting predisposition or protective effects to _S._ Typhi infection; other states were evident as early as 12 to 24 hours post challenge. These subsets are candidates to predict infection outcome at early stages of infection. 

Deciphering the imune subsets in Salmonells Tyhi human infection which underly disease out come

Exploring the intricacies of host-pathogen communication is vital in order to understand why
some microbes persist within a host, while others are effectively cleared. As such,
host-pathogen communication is an urgent area of research underpinning human health
and disease, especially given the emerging concerns of antibiotic resistance.
Understanding host-pathogen pathways requires intricate knowledge in the fields of both
microbiology and immunology.

Living in a world of specialists, where scientists sometimes invest their whole career
studying one organism, a specific pathway or a protein, multidisciplinary discussions of
host-pathogen interactions are highly needed. This international conference will provide
such a forum for scientific exchange at the highest level, between scientists from different
research areas related to host-pathogen interactions, with the aim to trigger fruitful
collaborations addressing the urgent questions in the field.

This meeting has an additional special focus of bringing researchers from Ireland, Denmark
and Israel together to learn about cutting edge biology and form new collaborations.
Thus, the conference will be a showcase for the exciting and original research emanating
from these three small but innovative countries.

Host-Pathogen Communication (HPC) 2021

Helminths battle type 2 immunity for control of the intestinal stem cell niche