One of the main features of the immune response toM. Tuberculosisis the formation of an organized structure called granuloma. It consists mainly in the recruitment at the infectious stage of macrophages, highly differentiated cells such as multinucleated giant cells, epithelioid cells and Foamy cells, all these cells being surrounded by a rim of lymphocytes. Although in the first instance the granuloma acts to constrain the infection, some bacilli can actually survive inside these structures for a long time in a dormant state. For some reasons, which are still unclear, the bacilli will reactivate in 10% of the latently infected individuals, escape the granuloma and spread throughout the body, thus giving rise to clinical disease, and are finally disseminated throughout the environment. In this review we examine the process leading to the formation of the granulomatous structures and the different cell types that have been shown to be part of this inflammatory reaction. We also discuss the differentin vivoandin vitromodels available to study this fascinating immune structure.

Two siblings with interleukin-12 receptor β1 (IL-12Rβ1) deficiency but different clinical phenotypes were studied. Both are homozygous for an IL12RB1

Since the emergence of COVID-19, many publications have reported associations with ABO blood types. Despite between-study discrepancies, an overall consensus has emerged whereby blood group O appears associated with a lower risk of COVID-19, while non-O blood types appear detrimental. Two major hypotheses may explain these findings: First, natural anti-A and anti-B antibodies could be partially protective against SARS-CoV-2 virions carrying blood group antigens originating from non-O individuals. Second, O individuals are less prone to thrombosis and vascular dysfunction than non-O individuals and therefore could be at a lesser risk in case of severe lung dysfunction. Here, we review the literature on the topic in light of these hypotheses. We find that between-study variation may be explained by differences in study settings and that both mechanisms are likely at play. Moreover, as frequencies of ABO phenotypes are highly variable between populations or geographical areas, the ABO coefficient of variation, rather than the frequency of each individual phenotype is expected to determine impact of the ABO system on virus transmission. Accordingly, the ABO coefficient of variation correlates with COVID-19 prevalence. Overall, despite modest apparent risk differences between ABO subtypes, the ABO blood group system might play a major role in the COVID-19 pandemic when considered at the population level.

Enveloped viruses are glycosylated, meaning that their envelope proteins are post-translationally modified by the addition of glycans. Some glycosyltransferases that contribute to terminate glycan chains synthesis are differentially expressed between cell types within or between species, which bears important immunological consequences [1]. A prime example concerns the GGTA1 gene encoding a galactosyltransferase that catalyzes the transfer of a galactose in α1,3 linkage onto subterminal N-acetyllactosamines. This glycosyltransferase is expressed by all mammals except Old World monkeys, apes and humans, due to inactivating mutations that occurred in a common primate ancestor some 20 to 40 million years ago. Consequently, all humans lack the αGal glycan motif and possess natural anti-αGal antibodies generated in response to bacteria of the microbiota that express similar glycans [2]. Likewise, humans lack expression of the N-glycolyl form of sialic acid (NeuGc) due to a pseudogenization event of the CMAH gene that occurred about 2 million years ago. In most other animal species, the orthologous gene encodes the cytidine monophosphate (CMP)-NeuAc hydroxylase that converts NeuAc into NeuGc from the nucleotide form CMP-NeuAc. As a result of our inability to synthesize NeuGc, natural anti-NeuGc are also present in humans (reviewed in [3,4]). Another example concerns the enzymes that are involved in the synthesis of the ABO histo-blood group antigens. The A and B enzymes catalyze the transfer of an N-acetylgalactosamine and a galactose, respectively, in α1,3 linkage on a precursor structure called the H antigen, generating the corresponding A or B antigens. They are encoded by distinct alleles at the ABO locus. The O alleles are null alleles responsible for a lack of transferase, in which case the H antigen remains unchanged. O alleles in the homozygote state confer blood group O, which is characterized by a complete absence of A or B antigens [5]. Under stimulation by bacteria of the microbiota that present glycan motifs similar to either A or B antigens, blood group O people develop so-called "natural" anti-A and anti-B antibodies, whilst blood group A and B individuals develop either anti-B or anti-A antibodies, respectively [6]. Only people of the AB subgroup lack such antibodies. In humans, besides their expression on red blood cells, ABH antigens are widely expressed on many other cell types, including vascular endothelial cells and epithelial cells of many organs [7]. Importantly, the titers of anti-αGal, anti-NeuGc, and anti-A/B antibodies are highly variable between individuals, ranging from 100-to 1000-fold [8,9]. When enveloped viruses are produced by cells expressing these glycan epitopes, they can be effectively neutralized by anti-αGal or anti-A and anti-B antibodies as shown for several animal and human enveloped viruses (reviewed in[2]). Coronavirus S protein trimers are covered by an extensive glycan shield made of N-linked glycans that surrounds the receptor-binding

Susceptibility to Covid-19 has been found to be associated with the ABO blood group, with O type individuals being at a lower risk. However, the underlying mechanism has not been elucidated. Here, we aimed to test the hypothesis that Covid-19 patients might have lower levels of ABO antibodies than non-infected individuals as they could offer some degree of protection. After showing that the viral spike protein harbors the ABO glycan epitopes when produced by cells expressing the relevant glycosyltransferases, like upper respiratory tract epithelial cells, we enrolled 290 patients with Covid-19 and 276 asymptomatic controls to compare their levels of natural ABO blood group antibodies. We found significantly lower IgM anti-A + anti-B agglutination scores in blood group O patients (76.93 vs 88.29, P-value = 0.034) and lower levels of anti-B (24.93 vs 30.40, P-value = 0.028) and anti-A antibodies (28.56 vs 36.50, P-value = 0.048) in blood group A and blood group B patients, respectively, compared to controls. In this study, we showed that ABO antibody levels are significantly lower in Covid-19 patients compared to controls. These findings could indicate that patients with low levels of ABO antibodies are at higher risk of being infected.

Carcinoma-associated fucosylated antigens are markers of the epithelial state and can contribute to cell adhesion through CLEC17A (Prolectin)