A novel approach to single-cell analysis reveals intrinsic differences in immune marker expression in unstimulated BALB/c and C57BL/6 macrophages

The origin of functional heterogeneity among macrophages, key innate immune system components, is still debated. While mouse strains differ in their immune responses, the range of gene expression variation among their pre-stimulation macrophages is unknown. With a novel approach to scRNA-seq analysis, we reveal the gene expression variation in unstimulated macrophage populations from BALB/c and C57BL/6 mice. We show that intrinsic strain-to-strain differences are detectable before stimulation and we place the unstimulated single cells within the gene expression landscape of stimulated macrophages. C57BL/6 mice show stronger evidence of macrophage polarization than BALB/c mice, which may contribute to their relative resistance to pathogens. Our computational methods can be generally adopted to uncover biological variation between cell populations

Nutrition Knowledge, Personal Motivation, And Food Label Use Among Indian Adults With Multiple Chronic Conditions: A Moderated Mediation Model.

Background: There has been little research conducted within developing nations examining the link between knowledge and diet-related perceptions and behaviors. In addition, prior investigations have rarely examined interrelationships between knowledge and other nutrition-related factors. Purpose: This study explored the relationship between nutrition knowledge, social/informational factors, and diet-related outcomes among Indian adults with multiple chronic conditions. Methods: A snowball sampling technique was employed to recruit individuals. Hierarchical regression analysis was employed to examine mediating and moderating relationships. Results: Results from a cross-sectional survey indicated that knowledge only predicted use among those reporting greater pressure/concern from close others. Furthermore, social support and social trust were found to moderate the relationship between knowledge and diet-related perceptions and behaviors. Discussion: Results suggest that social factors may play a critical role in moderating the impact of nutritionknowledge on diet-related perceptions and behaviors. Translation to Health Education Practice: Public Health Education interventions targeting developing nations should aim to maximize consumers\u27 nutritionknowledge while identifying valued close others who can help encourage positive health action. Furthermore, Health Educators as well as government and local communities must engage in outreach efforts to reinforce or, if necessary, change public perceptions regarding the food industry

An evolutionarily conserved coronin-dependent pathway defines cell population size

Maintenance of cell population size is fundamental to the proper functioning of multicellular organisms. Here, we describe a cell-intrinsic cell density-sensing pathway that enabled T cells to reach and maintain an appropriate population size. This pathway operated "kin-to-kin" or between identical or similar T cell populations occupying a niche within a tissue or organ, such as the lymph nodes, spleen, and blood. We showed that this pathway depended on the cell density-dependent abundance of the evolutionarily conserved protein coronin 1, which coordinated prosurvival signaling with the inhibition of cell death until the cell population reached threshold densities. At or above threshold densities, coronin 1 expression peaked and remained stable, thereby resulting in the initiation of apoptosis through kin-to-kin intercellular signaling to return the cell population to the appropriate cell density. This cell population size-controlling pathway was conserved from amoeba to humans, thus providing evidence for the existence of a coronin-regulated, evolutionarily conserved mechanism by which cells are informed of and coordinate their relative population size

Disruption of Coronin 1 Signaling in T Cells Promotes Allograft Tolerance while Maintaining Anti-Pathogen Immunity

The ability of the immune system to discriminate self from non-self is essential for eradicating microbial pathogens but is also responsible for allograft rejection. Whether it is possible to selectively suppress alloresponses while maintaining anti-pathogen immunity remains unknown. We found that mice deficient in coronin 1, a regulator of naive T cell homeostasis, fully retained allografts while maintaining T cell-specific responses against microbial pathogens. Mechanistically, coronin 1-deficiency increased cyclic adenosine monophosphate (cAMP) concentrations to suppress allo-specific T cell responses. Costimulation induced on microbe-infected antigen presenting cells was able to overcome cAMP-mediated immunosuppression to maintain anti-pathogen immunity. In vivo pharmacological modulation of this pathway or a prior transfer of coronin 1-deficient T cells actively suppressed allograft rejection. These results define a coronin 1-dependent regulatory axis in T cells important for allograft rejection and suggest that modulation of this pathway may be a promising approach to achieve long-term acceptance of mismatched allografts

Anthrax: Biology of Bacillus anthracis

Perhaps no other microorganism has received as much attention for its use as a potential agent for bioterrorism as Bacillus anthracis. In spite of the fact that the organism has been known for a very long time, limited progress has been made in developing a vaccine or understanding its biochemical and genetic properties. The genus Bacillus includes aerobic bacilli forming heat-resistant spores. B. anthracis are the only non-motile and the most pathogenic bacilli in this genus. Pulmonary anthrax can be caused by inhalation of just 10,000 spores of anthrax and is fatal unless treated immediately with antibiotics. Anthrax is actually a disease of herbivorous animals with humans getting infected by spores due to accidental entry into the body by contact with infected animals or contaminated animal products, insect bites, inhalation or ingestion. This lethality is principally due to the polysaccharide capsule that helps the bacterium to evade immune attack and the tripartite toxin that can kill the host depending on the mode of entry of the bacillus into the host and the host’s immune status

Regulation of immune cell homeostasis and function by coronin 1

Coronin 1 is the most recent candidate in the list of genes causing severe combined immunodeficiency (SCID) in humans. A distinctive feature of the SCID induced by coronin 1 deficiency is selective naïve T cell lymphopenia in the presence of a normal thymus as well as normal B cell and natural killer cell numbers (T(-)B(+)NK(+)). Coronin 1 is a member of the evolutionarily conserved coronin protein family, members of which are widely expressed across the eukaryotic kingdom. Mammals express seven coronin molecules, numbered from coronin 1 to 7. The different coronin proteins have a distinct but overlapping tissue expression and have been reported to be involved in a wide array of cellular functions including calcium homeostasis, cytoskeletal dynamics, immune and inflammatory responses, neuromuscular transmission as well as cognition and behavior. In this minireview, we describe the role of coronin 1 in the maintenance of immune cell diversity and function

Subversion of host immune responses by Mycobacterium tuberculosis

Tuberculosis, one of the world's oldest diseases has nowadays reached a pandemic prevalence. Despite its long history and intense research, efficient drugs against its causative agent, M. tuberculosis, are still limited. One reason for the pathogen's success lies within its capability to evade host immune defense mechanisms and to create a niche within host cells enabling the bacterium to persist for long periods. M. tuberculosis has evolved a diversified set of strategies to manipulate the immune response of the host. In this communication, we discuss some of the strategies employed by M. tuberculosis in order to survive within the hostile environment of the macrophage. A detailed analysis of the molecular basis of host-pathogen interactions will unravel novel mechanisms and might contribute to finding novel approaches to treat and combat tuberculosis

Induction of allograft tolerance while maintaining immunity against microbial pathogens: does coronin 1 hold a key?

Selective suppression of graft rejection while maintaining anti-pathogen responses has been elusive. Thus far, the most successful strategies to induce suppression of graft rejection relies on inhibition of T cell activation. However, the very same mechanisms that induce allograft-specific T cell suppression are also important for immunity against microbial pathogens as well as oncogenically transformed cells, resulting in significant immunosuppression-associated comorbidities. Therefore, defining the pathways that differentially regulate anti-graft versus anti-microbial T cell responses may allow the development of regimen to induce allograft-specific tolerance. Recent work has defined a molecular pathway driven by the immunoregulatory protein coronin 1 that regulates the phosphodiesterase/cAMP pathway and modulates T cell responses. Interestingly, disruption of coronin 1 promotes allograft tolerance while immunity towards a range of pathogenic microbes is maintained. Here, we briefly review the work leading up to these findings as well as their possible implications for transplantation medicine

Elimination of intracellularly residing Mycobacterium tuberculosis through targeting of host and bacterial signaling mechanisms

With more than 2 billion latently infected people, TB continues to represent a serious threat to human health. According to the WHO, 1.1 million people died from TB in 2010, which is equal to approximately 3000 deaths per day. The causative agent of the disease, Mycobacterium tuberculosis, is a highly successful pathogen having evolved remarkable strategies to persist within the host. Although normally, upon phagocytosis by macrophages, bacteria are readily eliminated by lysosomes, pathogenic mycobacteria actively prevent destruction within macrophages. The strategies that pathogenic mycobacteria apply range from releasing virulence factors to manipulating host molecules resulting in the modulation of host signal transduction pathways in order to sustain their viability within the infected host. Here, we analyze the current status of how a better understanding of both the bacterial and host factors involved in virulence can be used to develop drugs that may be helpful to curb the TB epidemic

Interference of <i style="">Mycobacterium tuberculosis</i> with macrophage responses

401-406Tuberculosis, caused by Mycobacterium tuberculosis, has become an important health and economic burden, with more than four thousand people succumbing to the disease every day. Thus, there is an urgent need to understand the molecular basis of this pathogen’s success in causing disease in humans, in order to develop new drugs superior to conventional drugs available at present. One reason why M. tuberculosis is such a dangerous microbe lies within its ability to survive within infected hosts, thereby efficiently circumventing host immune responses. Over the past few years, a number of mechanisms have been unravelled that are utilized by M. tuberculosis to survive within hosts and to avoid immune defence mechanisms. Several of these mechanisms have been described in this communication that may be useful for the development of novel compounds to treat tuberculosis