The dogma that adaptive immunity is the only arm of the immune response with memory capacity has been recently challenged by several studies demonstrating evidence for memory-like innate immune ...training. However, the underlying mechanisms and location for generating such innate memory responses in vivo remain unknown. Here, we show that access of Bacillus Calmette–Guérin (BCG) to the bone marrow (BM) changes the transcriptional landscape of hematopoietic stem cells (HSCs) and multipotent progenitors (MPPs), leading to local cell expansion and enhanced myelopoiesis at the expense of lymphopoiesis. Importantly, BCG-educated HSCs generate epigenetically modified macrophages that provide significantly better protection against virulent M. tuberculosis infection than naïve macrophages. By using parabiotic and chimeric mice, as well as adoptive transfer approaches, we demonstrate that training of the monocyte/macrophage lineage via BCG-induced HSC reprogramming is sustainable in vivo. Our results indicate that targeting the HSC compartment provides a novel approach for vaccine development.
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•Access of BCG to the bone marrow expands HSCs and promotes myelopoiesis•BCG educates HSCs to generate trained monocytes/macrophages•BCG induces a unique epigenetic and transcriptomic signature in macrophages•BCG-trained macrophages are highly protective against pulmonary M. tuberculosis infection
BCG induces trained immunity through education of hematopoietic stem cells.
The current study investigates incompressible, MHD flow of Cross nanofluid containing of gyrotactic microorganisms and thermophoretic particle deposition over a sheet with activation energy and ...variable thermal conductivity. The variable characteristic of thermal conductivity is considered as a linear function of temperature. The present study’s insights can optimize the design of nanofluid-based systems, enhance drug delivery methods, improve environmental monitoring, refine materials engineering, advance microfluidics for diagnostics, boost renewable energy technologies, and upgrade electronics cooling solutions. Moreover, this study contribution to scientific understanding will catalyze further research across disciplines, fostering innovation and progress. Cross nanofluid containing iron oxide
(
F
e
3
O
4
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nanoparticles, and based fluid ethylene glycol (
C
2
H
6
O
2
)
is used. In the current study, distributions of concentration, temperature, mass, microorganisms, and flow are examined in the presence of nanofluid while also accounting for thermophoretic particle deposition and a heat source. The proposed flow equations are transmuted into ODEs by employing the suitable similarity variables. RKF-45th approach is used to evaluate the reduced equations. Graphs are used to determine the effects of important factors on thermal, microorganism, concentration, and flow profiles. With a rise in the Marangoni ratio parameter, the velocity distribution is enhanced, whereas the temperature distribution exhibit inverse behavior.
A greater understanding of hematopoietic stem cell (HSC) regulation is required for dissecting protective versus detrimental immunity to pathogens that cause chronic infections such as Mycobacterium ...tuberculosis (Mtb). We have shown that systemic administration of Bacille Calmette-Guérin (BCG) or β-glucan reprograms HSCs in the bone marrow (BM) via a type II interferon (IFN-II) or interleukin-1 (IL1) response, respectively, which confers protective trained immunity against Mtb. Here, we demonstrate that, unlike BCG or β-glucan, Mtb reprograms HSCs via an IFN-I response that suppresses myelopoiesis and impairs development of protective trained immunity to Mtb. Mechanistically, IFN-I signaling dysregulates iron metabolism, depolarizes mitochondrial membrane potential, and induces cell death specifically in myeloid progenitors. Additionally, activation of the IFN-I/iron axis in HSCs impairs trained immunity to Mtb infection. These results identify an unanticipated immune evasion strategy of Mtb in the BM that controls the magnitude and intrinsic anti-microbial capacity of innate immunity to infection.
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•BCG and Mtb uniquely reprogram HSCs for at least 1 year•Mtb suppresses myelopoiesis and impairs HSC engraftment•Mtb hijacks a type I IFN/iron axis to induce necroptosis specifically in myeloid lineage•Reprogramming of HSCs by a type I IFN/iron axis impairs trained immunity
The pathogen Mycobacterium tuberculosis reprograms hematopoietic stem cells and limits myelopoiesis while impairing trained immunity responses via a type I IFN/iron signaling axis.
This study discusses the flow of hybrid nanofluid over an infinite disk in a Darcy-Forchheimer permeable medium with variable thermal conductivity and viscosity. The objective of the current ...theoretical investigation is to identify the thermal energy characteristics of the nanomaterial flow resulting from thermo-solutal Marangoni convection on a disc surface. By including the impacts of activation energy, heat source, thermophoretic particle deposition and microorganisms the proposed mathematical model becomes more novel. The Cattaneo-Christov mass and heat flux law is taken into account when examining the features of mass and heat transmission rather than the traditional Fourier and Fick heat and mass flux law. MoS
and Ag nanoparticles are dispersed in the base fluid water to synthesize the hybrid nanofluid. PDEs are transformed to ODEs by using similarity transformations. The RKF-45th order shooting method is used to solve the equations. With the use of appropriate graphs, the effects of a number of non-dimensional parameters on velocity, concentration, microorganism, and temperature fields are addressed. The local Nusselt number, density of motile microorganisms and Sherwood number are calculated numerically and graphically to derive correlations in terms of the relevant key parameters. The findings show that as we increase the Marangoni convection parameter, skin friction, local density of motile microorganisms, Sherwood number, velocity, temperature and microorganisms profiles increase, whereas Nusselt number and concentration profile exhibit an opposite behavior. The fluid velocity is reduced as a result of enhancing the Forchheimer parameter and Darcy parameter.
β-glucan is a potent inducer of epigenetic and functional reprogramming of innate immune cells, a process called “trained immunity,” resulting in an enhanced host response against secondary ...infections. We investigate whether β-glucan exposure confers protection against pulmonary Mycobacterium tuberculosis (Mtb) infection. β-glucan induces trained immunity via histone modifications at gene promoters in human monocytes, which is accompanied by the enhanced production of proinflammatory cytokines upon secondary Mtb challenge and inhibition of Mtb growth. Mice treated with β-glucan are significantly protected against pulmonary Mtb infection, which is associated with the expansion of hematopoietic stem and progenitor cells in the bone marrow and increased myelopoiesis. The protective signature of β-glucan is mediated via IL-1 signaling, as β-glucan shows no protection in mice lacking a functional IL-1 receptor (IL1R−/−). The administration of β-glucan may be used as a novel strategy in the treatment of mycobacterial infections and possibly as an adjuvant to improve anti-tuberculosis vaccines.
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•β-glucan induces protective trained immunity in human monocytes infected with Mtb•β-glucan induces protective trained immunity in mice infected with Mtb•β-glucan-mediated protection against Mtb is dependent on IL-1 signaling•β-glucan increases expansion of hematopoietic progenitors and myelopoiesis via IL-1
Moorlag et al. show that β-glucan induces protective trained immunity in human monocytes and in mice infected with virulent Mtb. β-glucan-mediated protection against Mtb is dependent on IL-1 signaling and is associated with the expansion of hematopoietic stem and progenitor cells in the bone marrow and increased myelopoiesis.
Marangoni convection is discovered by varying gradients of surface tension. Marangoni induced flow plays a vital role in melting of coating flow technology, drying wafers, crystals, soap film ...stabilization, wielding and microfluidics, in which the flow creates unwanted impacts under gravity on micro-level in the same manner as buoyancy-induced natural convection. The Magneto-Marangoni convective flow of Walter-B fluid over a vertical permeable surface is addressed in the current research. The Dufour–Soret effects are taken into account along with activation energy and radiation. Flow through a porous media is modeled via Darcy and Forchheimer theory. The surface tension gradient becomes stronger by increasing the Marangoni convection parameter, which results in stronger induced flows and more efficient heat and mass movement inside the liquid. The result is a more uniform distribution of these qualities throughout the liquid as the temperature and concentration profiles drop. With higher viscoelastic parameter levels, the fluid accelerates and the velocity profile increases due to decreased viscosity. Due to an augmentation in the Dufour and Soret number, the thermal and concentration of the Walter-B fluid boost up respectively.
Abstract
The recent work investigates the heat transfer attributes in the flow of engine oil which comprises of nano-particles such as Cu and TiO
2
. The performance of Copper and Titanium oxide is ...over looked in the flow of engine oil. The energy equation is amended by the features of thermal radiation, viscous dissipation, and heat generation. The mathematical model signifies the porosity, entropy generation and moving flat horizontal surface with the non-uniform stretching velocity. Quasi-linearization, which is a persuasive numerical technique to solve the complex coupled differential equations, is used to acquire the numerical solution of the problem. Flow and heat transfer aspects of Cu–TiO
2
in the flow are examined against the preeminent parameters. The flow is significantly affected by the thermal jump conditions and porous media. It is observed here that the temperature as well as heat transport rate is reduced with the effect of involved preeminent parameters. However, such fluids must be used with caution in applications where a control on the heat transfer is required. We may conclude that the recent study will provide assistance in thermal cooling systems such as engine and generator cooling, nuclear system cooling, aircraft refrigeration system, and so forth.
In present investigation, the axisymmetric analysis for the Casson nano-material has been analyzed due to two parallel stretchable disks. The novel thermophoresis and Brownian aspects of nanofluid ...are studied by using Buongiorno nanofluid model. Similarity transformations are applied on the system of governing equations that renovate it into the problem into proper dimensionless form. The homotopic procedure is suggested for the determination of solution. The role of numerous parameters on dimensionless velocity and temperature are observed in very effective way. To study the effect of Brownian motion and thermophoresis diffusion parameter, Buongiorno model is adopted. Radial and axial velocity profile has increasing behavior for stretching ratio and Casson parameter. As the value of Biot number and thermophoresis parameter enhanced, the concentration profile also enhances and concentration profile declines due to increase in value of Brownian motion parameter. Temperature profile decreases as the value of Reynolds number and Prandtl number increased. The values of Sherwood number, Nusselt number and Skin friction are calculated at upper and lower disk to understand the behavior of stretching disks.
Owing to the widespread practical significances of nanoparticles in thermal engineering and industrial processes, scientists are devoted to explore the more fundamental thermal aspects of such ...nano-materials. Recently, the nanoparticles show extensive applications in heat transfer improvement, energy production, cooling and heating processes, refrigeration, thermal extrusion processes, thermoelectric devices, bio-medical applications like cancer treatment, brain tumors and many more. Moreover, the phenomenon of bioconvection utilize interesting applications in bio-technology, bio-fuels, enzymes, fertilizes etc. Keeping such motivations in mind, this research presents the bioconvection flow of nanofluid induced by two stretchable disks separated at confined distance. The Buongiorno nanofluid model is employed to examine the Brownian motion and thermophoresis aspects. The equations govern for the flow of the nanofluid, heat transfer; nanoparticles concentration and density of motile microorganisms’ fields are simplified with the help of similarity transformation. The resultant form of nonlinear equations is solved by using homotopy analysis method. The influence of significantly participating parameters on velocity, nanofluid temperature, concentration and density of motile microorganisms profiles are observed with relevant physical significances. The convergence of solution for velocity, temperature, concentration and motile microorganisms profiles are examined carefully. The simulations are compared with already declared numerical data and found a convincible accuracy. It is noticed that the temperature profile enhances up to specified range and then start decline due to larger values of values of Brownian motion and thermophoresis parameters. A dual nature of velocity profiles for higher the value of stretching parameter has been observed. The concentration profile declines with increasing Brownian motion constant and Lewis number. The motile microorganisms profile decreases due to enhancement of bio-convection Peclet number, Reynolds number and Schmidt number.
Host defense strategies against infectious diseases are comprised of both host resistance and disease tolerance. Resistance is the ability of the host to prevent invasion or to eliminate the ...pathogen, while disease tolerance is defined by limiting the collateral tissue damage caused by the pathogen and/or the immune response without exerting direct effects on pathogen growth. Our incomplete understanding of host immunity against tuberculosis (TB) is predominately rooted in our bias toward investigating host resistance. Thus, we must refocus our efforts to understand the entire spectrum of immunity against
to control TB.
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