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Toll-like Receptor 2 in Autoimmune Inflammation

Marks Kathryne E.,Cho Kaylin,Stickling Courtney,Reynolds Joseph M. 대한면역학회 2021 Immune Network Vol.21 No.3
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TLR signaling is critical for broad scale immune recognition of pathogens and/or danger molecules. TLRs are particularly important for the activation and the maturation of cells comprising the innate immune response. In recent years it has become apparent that several different TLRs regulate the function of lymphocytes as well, albeit to a lesser degree compared to innate immunity. TLR2 heterodimerizes with either TLR1 or TLR6 to broadly recognize bacterial lipopeptides as well as several danger-associated molecular patterns. In general, TLR2 signaling promotes immune cell activation leading to tissue inflammation, which is advantageous for combating an infection. Conversely, inappropriate or dysfunctional TLR2 signaling leading to an overactive inflammatory response could be detrimental during sterile inflammation and autoimmune disease. This review will highlight and discuss recent research advances linking TLR2 engagement to autoimmune inflammation.
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Molecular Surveillance Identifies Multiple Transmissions of Typhoid in West Africa

Wong, Vanessa K.,Holt, Kathryn E.,Okoro, Chinyere,Baker, Stephen,Pickard, Derek J.,Marks, Florian,Page, Andrew J.,Olanipekun, Grace,Munir, Huda,Alter, Roxanne,Fey, Paul D.,Feasey, Nicholas A.,Weill, F Public Library of Science 2016 PLoS neglected tropical diseases Vol.10 No.9
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<▼1>BackgroundThe burden of typhoid in sub-Saharan African (SSA) countries has been difficult to estimate, in part, due to suboptimal laboratory diagnostics. However, surveillance blood cultures at two sites in Nigeria have identified typhoid associated with Salmonella enterica serovar Typhi (S. Typhi) as an important cause of bacteremia in children.MethodsA total of 128 S. Typhi isolates from these studies in Nigeria were whole-genome sequenced, and the resulting data was used to place these Nigerian isolates into a worldwide context based on their phylogeny and carriage of molecular determinants of antibiotic resistance.ResultsSeveral distinct S. Typhi genotypes were identified in Nigeria that were related to other clusters of S. Typhi isolates from north, west and central regions of Africa. The rapidly expanding S. Typhi clade 4.3.1 (H58) previously associated with multiple antimicrobial resistances in Asia and in east, central and southern Africa, was not detected in this study. However, antimicrobial resistance was common amongst the Nigerian isolates and was associated with several plasmids, including the IncHI1 plasmid commonly associated with S. Typhi.ConclusionsThese data indicate that typhoid in Nigeria was established through multiple independent introductions into the country, with evidence of regional spread. MDR typhoid appears to be evolving independently of the haplotype H58 found in other typhoid endemic countries. This study highlights an urgent need for routine surveillance to monitor the epidemiology of typhoid and evolution of antimicrobial resistance within the bacterial population as a means to facilitate public health interventions to reduce the substantial morbidity and mortality of typhoid.</▼1><▼2>Author SummaryTyphoid fever, a serious bloodstream infection caused by the bacterium Salmonella Typhi, is a major cause of disease and death around the world. There have been limited data on the epidemiology of typhoid in many countries in sub-Saharan African, including Nigeria. Recent evidence, however, showed that typhoid was an important cause of bacteraemia in children residing in two regions of Nigeria. Here, we analyzed the whole genome sequences of 128 S. Typhi isolates from two studies in order to elucidate the population structure and characterize the genetic components of antimicrobial resistance. We found that the multiple S. Typhi genotypes identified were closely related to other S. Typhi from neighboring regions of Africa and that multidrug resistance (MDR) was common among these isolates, and in many cases was associated with the IncHI1 plasmid known to cause MDR typhoid. These results provide evidence that typhoid was established in Nigeria as a result of several independent introductions into the country and that there has been extensive exchange of S. Typhi in and around the region of West Africa. This study emphasizes the importance of surveillance to improve our understanding of the epidemiology of typhoid, which is needed to underpin public health measures to reduce the spread of disease and facilitate patient management.</▼2>

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