The hygiene hypothesis and the increasing prevalence of chronic inflammatory disorders

PLoS ONE, 2011

The environmental mycobacterium, M. vaccae has been used in mouse models to support the contemporary hygiene hypothesis that non-pathogenic microorganisms reduce allergy associated T helper (Th)2 responses and inflammatory diseases by augmenting regulatory T cells. However, data for human models and possible mechanisms are limited. We tested the effect of innate immune interactions between human DC and M. vaccae on DC-dependent T cell responses. M. vaccae activation of DC via Toll like receptor (TLR)2 was compared to a specific TLR2 ligand (Pam 3 CSK4) and alternative stimulation with a TLR4 ligand (LPS). M. vaccae induced DC dependent inhibition of Th2 responses, in contrast to Pam 3 CSK4, which had the opposite effect and LPS, which had no polarizing effect. DC maturation, gene expression and cytokine production, in response to each stimulus did not correlate with the specific functional effects. Comparable DC transcriptional responses to M. vaccae and Pam 3 CSK4 suggested that TLR2 mediated transcriptional regulation was not sufficient for inhibition of Th2 responses. Transcription factor enrichment analysis and assessment of signaling events, implicated a role for selective early activation of the CREB pathway by M. vaccae. Further study of the CREB pathway may provide novel insight into the molecular mechanisms of DC-dependent T cell polarization.

International Journal of Cancer, 2009

Allergy/atopy has been suggested to protect against non-Hodgkin lymphoma (NHL) and specific IgE levels are decreased in patients with NHL. We speculated that all immunoglobulin subclass levels might be downregulated in NHL and examined levels of IgM, IgD, IgA, IgE, IgG and IgG 4 in 200 NHL patients and 200 age-and sexmatched controls. Patients with B-cell NHL of many types had consistently lower median immunoglobulin subclass levels than controls. In every subclass except IgD, about 10-15% of B-cell NHL patients had absolute levels below the 2.5 percentile of controls. Subclass levels correlated with each other and many patients had more than one significantly low level. Levels were lowest for IgG 4 and IgE. Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma had especially low total IgE levels. In other B-cell NHL types, total IgE levels were decreased to a similar extent as other immunoglobulin subclasses. In conclusion, low IgE levels are only part of a more generalized loss of immunoglobulins of all subtypes in a wide variety of B-cell NHL types. Low immunoglobulin levels appear to be a consequence of B-cell NHL presence, and we speculate about molecular mechanisms that could reduce all immunoglobulin subclasses in B-cell NHL. '

Frontiers in Microbiology

The prevalence of inflammatory bowel disease (IBD) has increased in Western countries during the course of the twentieth century, and is evolving to be a global disease. Recently we showed that a bacterial meal of a non-commensal, non-pathogenic methanotrophic soil bacterium, Methylococcus capsulatus Bath prevents experimentally induced colitis in a murine model of IBD. The mechanism behind the effect has this far not been identified. Here, for the first time we show that M. capsulatus, a soil bacterium adheres specifically to human dendritic cells, influencing DC maturation, cytokine production, and subsequent T cell activation, proliferation and differentiation. We characterize the immune modulatory properties of M. capsulatus and compare its immunological properties to those of another Gram-negative gammaproteobacterium, the commensal Escherichia coli K12, and the immune modulatory Gram-positive probiotic bacterium, Lactobacillus rhamnosus GG in vitro. M. capsulatus induces intermediate phenotypic and functional DC maturation. In a mixed lymphocyte reaction M. capsulatus-primed monocyte-derived dendritic cells (MoDCs) enhance T cell expression of CD25, the γ-chain of the high affinity IL-2 receptor, supports cell proliferation, and induce a T cell cytokine profile different from both E. coli K12 and Lactobacillus rhamnosus GG. M. capsulatus Bath thus interacts specifically with MoDC, affecting MoDC maturation, cytokine profile, and subsequent MoDC directed T cell polarization.

Scientific reports, 2018

The genetic architecture of asthma was relatively well explored. However, some work remains in the field to improve our understanding on asthma genetics, especially in non-Caucasian populations and with regards to commonly neglected genetic variants, such as Copy Number Variations (CNVs). In the present study, we investigated the contribution of CNVs on asthma risk among Latin Americans. CNVs were inferred from SNP genotyping data. Genome wide burden and association analyses were conducted to evaluate the impact of CNVs on asthma outcome. We found no significant difference in the numbers of CNVs between asthmatics and non-asthmatics. Nevertheless, we found that CNVs are larger in patients then in healthy controls and that CNVs from cases intersect significantly more genes and regulatory elements. We also found that a deletion at 6p22.1 is associated with asthma symptoms in children from Salvador (Brazil) and in young adults from Pelotas (Brazil). To support our results, we conducted...

Vaccines

Human lymphatic filariae have evolved numerous immune evasion strategies to secure their long-term survival in a host. These strategies include regulation of pattern recognition receptors, mimicry with host glycans and immune molecules, manipulation of innate and adaptive immune cells, induction of apoptosis in effector immune cells, and neutralization of free radicals. This creates an anti-inflammatory and immunoregulatory milieu in the host: a modified Th2 immune response. Therefore, targeting filarial immunomodulators and manipulating the filariae-driven immune system against the filariae can be a potential therapeutic and prophylactic strategy. Filariae-derived immunosuppression can also be exploited to treat other inflammatory diseases and immunopathologic states of parasitic diseases, such as cerebral malaria, and to prevent leishmaniasis. This paper reviews immunomodulatory mechanisms acquired by these filariae for their own survival and their potential application in the dev...

Expert Review of Vaccines, 2009

Vaccination is one of the most powerful health tools available owing to its ability to confer protection against various diseases. The long-term impact of such protection in terms of publichealth savings is nearly incalculable and becomes even more evident when considering if the vaccination concept is extended to the therapeutic potential of a given molecule. In this sense, DNA vaccines are especially important tools with enormous potential owing to the molecular precision that they offer. The properties of the plasmid DNA molecule in terms of stability, cost-effectiveness and lack of cold-chain requirement are additional advantages over traditional vaccines and therapeutics. We focus on the current knowledge of autoimmune mechanisms, engineering of DNA vaccines and attempts that have already been made in order to intervene in autoimmune processes. Our experience with a genetic vaccine containing the heat-shock protein gene (hsp65) from mycobacteria is also described.

Parasite immunology, 2018

Brazil is a middle-income country undergoing the epidemiological transition. Effects of changes in daily life habits, and access to clean water, sanitation and urban services on a growing urban population have contributed to a double burden of both infectious and non-communicable chronic diseases. Studies have indicated that parasite infections may modulate the human immune system and influence the development of allergic conditions such as asthma. However, there is no consensus in the published literature on the effects of parasitic infections on allergy, perhaps as a consequence of factors determining the epidemiology of these infections that vary between populations such as age of first infection, duration and chronicity of infections, parasite burden and species, and host genetic susceptibility. In this review, we discuss the observations from Brazil concerning the relationship between parasite infections and allergy. This article is protected by copyright. All rights reserved.

Arhivʺ vnutrennej mediciny, 2019

The aim of the study. To assess the significance of surrogate markers of the «hygienic hypothesis», the «old friends theory» and the hypothesis of «depletion of biomes» in the development of ulcerative colitis among the population of Western Siberia. Materials and methods: an active survey (interviewing) of 81 patients with ulcerative colitis and 39 healthy respondents was conducted. The main surrogate markers of the «hygienic theory», the hypotheses of «old friends» and «depletion of biomes» were studied: past infestations, pets in childhood, use of antibiotics, breastfeeding, family size (number of siblings), attendance at pre-school institutions, accommodation in a dormitory while studying, accommodation in a city or a village, type of drinking water supply and the type of water respondents use for drinking; in the framework of the «biome depletion» theory, in addition to the markers listed above, a sugar consumption rate was assessed. Consumption of simple carbohydrates was calculated based on the number of cups of tea and/or coffee drunk per week and the number of teaspoons or cubes of sugar that the respondent puts in one cup. Results. Among the indirect markers of the «hygiene hypothesis» and the theory of «old friends» examined, only one effect the risk of ulcerative colitis among the population of the Omsk region — visiting preschool institutions (2I = 4,59, p <0,05). Of the indirect signs of the «biome depletion» hypothesis examined, significant differences were found in the amount of simple carbohydrates consumed: patients with ulcerative colitis consumed more sugar with tea and/or coffee in the period before the first signs of the disease than healthy respondents (U = 1214,0; Z = 2,0; p = 0,04). Conclusion. In our study, the statistical significance of such factors as rare visits to kindergartens and the consumption of large amount of sugar by patients with ulcerative colitis in the period before the onset of the disease in comparison with healthy respondents was demonstrated.