Chlamydia pneumoniae Infection Induced Allergic Airway Sensitization Is Controlled by Regulatory T-Cells and Plasmacytoid Dendritic Cells

Chlamydia pneumoniae (CP) is associated with induction and exacerbation of asthma. CP infection can induce allergic airway sensitization in mice in a dose- and time-dependent manner. Allergen exposure 5 days after a low dose (mild-moderate), but not a high dose (severe) CP infection induces antigen sensitization in mice. Innate immune signals play a critical role in controlling CP infection induced allergic airway sensitization, however these mechanisms have not been fully elucidated. Wild-type, TLR2−/−, and TLR4−/− mice were infected intranasally (i.n.) with a low dose of CP, followed by i.n. exposure to human serum albumin (HSA) and challenged with HSA 2 weeks later. Airway inflammation, immunoglobulins, eosinophils, and goblet cells were measured. Low dose CP infection induced allergic sensitization in TLR2−/− mice, but not in TLR4−/− mice, due to differential Treg responses in these genotypes. TLR2−/− mice had reduced numbers of Tregs in the lung during CP infection while TLR4−/− mice had increased numbers. High dose CP infection resulted in an increase in Tregs and pDCs in lungs, which prevented antigen sensitization in WT mice. Depletion of Tregs or pDCs resulted in allergic airway sensitization. We conclude that Tregs and pDCs are critical determinants regulating CP infection-induced allergic sensitization. Furthermore, TLR2 and TLR4 signaling during CP infection may play a regulatory role through the modulation of Tregs

Low-level regulatory T-cell activity is essential for functional type-2 effector immunity to expel gastrointestinal helminths

Helminth infection is frequently associated with the expansion of regulatory T cells (Tregs) and suppression of immune responses to bystander antigens. We show that infection of mice with the chronic gastrointestinal helminth Heligmosomoides polygyrus drives rapid polyclonal expansion of Foxp3(+)Helios(+)CD4(+) thymic (t)Tregs in the lamina propria and mesenteric lymph nodes while Foxp3(+)Helios(-)CD4(+) peripheral (p)Treg expand more slowly. Notably, in partially resistant BALB/c mice parasite survival positively correlates with Foxp3(+)Helios(+)CD4(+) tTreg numbers. Boosting of Foxp3(+)Helios(+)CD4(+) tTreg populations by administration of recombinant interleukin-2 (rIL-2):anti-IL-2 (IL-2C) complex increased worm persistence by diminishing type-2 responsiveness in vivo, including suppression of alternatively activated macrophage and granulomatous responses at the sites of infection. IL-2C also increased innate lymphoid cell (ILC) numbers, indicating that Treg functions dominate over ILC effects in this setting. Surprisingly, complete removal of Tregs in transgenic Foxp3-DTR mice also resulted in increased worm burdens, with "immunological chaos" evident in high levels of the pro-inflammatory cytokines IL-6 and interferon-γ. In contrast, worm clearance could be induced by anti-CD25 antibody-mediated partial depletion of early Treg, alongside increased T helper type 2 responses and without incurring pathology. These findings highlight the overarching importance of the early Treg response to infection and the non-linear association between inflammation and the prevailing Treg frequency

Effect of wearing a helmet on the occurrence of head injuries in motorcycle riders in Benin: a case-control study

BACKGROUND: In Benin, motorcycles are the main means of transport for road users and are involved in more than half of crashes. This study aims to determine the effect of wearing a helmet on reducing head injuries in road crashes in Benin. METHODS: This case-control study took place in 2020 and focused on road trauma victims. The sample, consisting of 242 cases (trauma victims with head injuries) for 484 controls (without head injuries), was drawn from a database of traffic crash victims recruited from five hospitals across the country from July 2019 to January 2020. Four groups of independent variables were studied: socio-demographic and economic variables, history, behavioural variables including helmet use and road-related and environmental variables. To assess the shape of the association between the independent variables and the dependent variable, a descending step-by-step binary logistic regression model was performed using an explanatory approach. RESULTS: Fewer of the subjects with a head injury were wearing a helmet at the time of the crash 69.8% (95% CI = 63.6-75.6) compared to those without a head injury 90.3% (95% CI = 87.3-92.8). Adjusting for the other variables, subjects not wearing helmets were at greater risk of head injuries (OR = 3.8, 95% CI (2.5-5.7)); the head injury rating was 1.9 (95% CI = 1.2-3.3) times higher in subjects who were fatigued during the crash than among those who were not and 2.0 (95% CI = 1.2-3.3) times higher in subjects with no medical history. CONCLUSION: Failure to wear a helmet exposes motorcyclists to the risk of head injuries during crashes. It is important to increase awareness and better target such initiatives at the subjects most at risk

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

What can health inequalities researchers learn from an intersectionality perspective?:Understanding social dynamics with an inter-categorical approach

The concept of intersectionality was developed by social scientists seeking to analyse the multiple interacting influences of social location, identity and historical oppression. Despite broad take-up elsewhere, its application in public health remains underdeveloped. We consider how health inequalities research in the United Kingdom has predominantly taken class and later socioeconomic position as its key axis in a manner that tends to overlook other crucial dimensions. We especially focus on international research on ethnicity, gender and caste to argue that an intersectional perspective is relevant for health inequalities research because it compels researchers to move beyond (but not ignore) class and socioeconomic position in analysing the structural determinants of health. Drawing on these theoretical developments, we argue for an inter-categorical conceptualisation of social location that recognises differentiation without reifying social groupings – thus encouraging researchers to focus on social dynamics rather than social categories, recognising that experiences of advantage and disadvantage reflect the exercise of power across social institutions. Such an understanding may help address the historic tendency of health inequalities research to privilege methodological issues and consider different axes of inequality in isolation from one another, encouraging researchers to move beyond micro-level behaviours to consider the structural drivers of inequalities

Absence of Foxp3(+) regulatory T cells during allergen provocation does not exacerbate murine allergic airway inflammation

Regulatory T cells (Tregs) play a non-redundant role in maintenance of immune homeostasis. This is achieved by suppressing both, priming of naı¨ve cells and effector cell functions. Although Tregs have been implicated in modulating allergic immune responses, their influence on distinct phases of development of allergies remains unclear. In this study, by using bacterial artificial chromosome (BAC)-transgenic Foxp3-DTR (DEREG) mice we demonstrate that the absence of Foxp3+ Tregs during the allergen challenge surprisingly does not exacerbate allergic airway inflammation in BALB/c mice. As genetic disposition due to strain specificity may contribute significantly to development of allergies, we performed similar experiment in C57BL/6 mice, which are less susceptible to allergy in the model of sensitization used in this study. We report that the genetic background does not influence the consequence of this depletion regimen. These results signify the temporal regulation exerted by Foxp3+ Tregs in limiting allergic airway inflammation and may influence their application as potential therapeutics