Innate Immune Cell Function Research Articles

Opportunities for Nitric Oxide in Potentiating Cancer Immunotherapy.

Despite nearly 30 years of development and recent highlights of nitric oxide (NO) donors and NO delivery systems in anticancer therapy, the limited understanding of exogenous NO's effects on the immune system has prevented their advancement into clinical use. In particular, the effects of exogenously delivered NO differing from that of endogenous NO has obscured how the potential and functions of NO in anticancer therapy may be estimated and exploited despite the accumulating evidence of NO's cancer therapy-potentiating effects on the immune system. After introducing their fundamentals and characteristics, this review discusses the current mechanistic understanding of NO donors and delivery systems in modulating the immunogenicity of cancer cells as well as the differentiation and functions of innate and adaptive immune cells. Lastly, the potential for the complex modulatory effects of NO with the immune system to be leveraged for therapeutic applications is discussed in the context of recent advancements in the implementation of NO delivery systems for anticancer immunotherapy applications. SIGNIFICANCE STATEMENT: Despite a 30-year history and recent highlights of nitric oxide (NO) donors and delivery systems as anticancer therapeutics, their clinical translation has been limited. Increasing evidence of the complex interactions between NO and the immune system has revealed both the potential and hurdles in their clinical translation. This review summarizes the effects of exogenous NO on cancer and immune cells in vitro and elaborates these effects in the context of recent reports exploiting NO delivery systems in vivo in cancer therapy applications.

Roles of Vitamins in Immunity and COVID-19: A Literature Review

SARS-CoV-2 is a severe acute respiratory virus that causes Coronavirus Disease-19 (COVID-19). Even before the COVID-19 pandemic, diet was undeniably important in immunity. In order to be more resilient during and after the pandemic, understanding the role of vitamins is crucial. This review aims to explore the role of vitamins in supporting the immune system and its correlation to COVID-19. The article search was done using five electronic databases (i.e., Google Scholar, Semantic Scholar, ScienceDirect, PubMed, and PMC). Some of the keywords utilized in the literature search were “vitamin A and immunity” OR “vitamin B and immunity” OR “vitamin C and immunity” OR “vitamin D and immunity” OR “vitamin E and immunity”. A total of 51 articles was assessed in this literature review. Research finds vitamin A plays a role in both innate immune system cell function and humoral immunity by regulating, differentiating, and maturing immune system cells. Vitamin B complex primarily reduces inflammation by lowering serum C-reactive protein levels (CRP), while vitamin C strengthens epithelial barriers, phagocytes, T and B lymphocytes, and inflammatory mediators, to improve the immune system. Vitamin D acts as a mediator in the vitamin D receptor (VDR), an inner immune system component that regulates the humoral and adaptive immune systems through unique genetic transcriptions. Finally, vitamin E acts as an antioxidant, lowering the production of reactive oxygen and nitrogen species (ROS and RNS). In conclusion, all vitamins are essential in improving individual’s immune system that prevent from infectious diseases including COVID-19.

Impact of SARS-CoV-2 infection on the profiles and responses of innate immune cells after recovery.

BackgroundsSARS-CoV-2 infection results in a broad spectrum of clinical outcomes, ranging from asymptomatic to severe symptoms and death. Most COVID-19 pathogenesis is associated with hyperinflammatory conditions driven primarily by myeloid cell lineages. The long-term effects of SARS-CoV-2 infection post recovery include various symptoms.MethodsWe performed a longitudinal study of the innate immune profiles 1 and 3 months after recovery in the Thai cohort by comparing patients with mild, moderate, and severe clinical symptoms using peripheral blood mononuclear cells (n = 62).ResultsSignificant increases in the frequencies of monocytes compared to controls and NK cells compared to mild and moderate patients were observed in severe patients 1–3 months post recovery. Increased polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) were observed in all recovered patients, even after 3 months. Increased IL-6 and TNFα levels in monocytes were observed 1 month after recovery in response to lipopolysaccharide (LPS) stimulation, while decreased CD86 and HLA-DR levels were observed regardless of stimulation. A multiplex analysis of serum cytokines performed at 1 month revealed that most innate cytokines, except for TNFα, IL4/IL-13 (Th2) and IFNγ (Th1), were elevated in recovered patients in a severity-dependent manner. Finally, the myelopoiesis cytokines G-CSF and GM-CSF were higher in all patient groups. Increased monocytes and IL-6- and TNFα-producing cells were significantly associated with long COVID-19 symptoms.ConclusionsThese results reveal that COVID-19 infection influences the frequencies and functions of innate immune cells for up to 3 months after recovery, which may potentially lead to some of the long COVID symptoms.

The Innate and Adaptive Immune Cells in Alzheimer's and Parkinson's Diseases.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative disorders of the central nervous system (CNS). Increasing evidence supports the view that dysfunction of innate immune cells initiated by accumulated and misfolded proteins plays essential roles in the pathogenesis and progression of these diseases. The TLR family was found to be involved in the regulation of microglial function in the pathogenesis and progression of AD or PD, making it as double-edged sword in these diseases. Altered function of peripheral innate immune cells was found in AD and PD and thus contributed to the development and progression of AD and PD. Alteration of different subsets of T cells was found in the peripheral blood and CNS in AD and PD. The CNS-infiltrating T cells can exert both neuroprotective and neurotoxic effects in the pathogenesis and progression. Here, we review recent evidences for the roles of innate and adaptive immune cells in the pathogenesis and progression of AD and PD.

The effect of age on the clinical characteristics and innate immune cell function in the patients with abdominal sepsis.

Sepsis is a life-threatening dysregulated host response to infection that compromises organ health, and abdominal sepsis is a commonly presenting critical illness in intensive care units (ICU). In this study, we investigate the effect of age on clinical sepsis characteristics and innate immune cells (neutrophils and monocytes) functionality in abdominal sepsis patients. We recruited 32 patients with abdominal sepsis from the Beijing Ditan Hospital’s ICU from February 2021 to September 2021, and selected 18 healthy volunteers that were age- and sex-matched as controls for a prospective cohort study. Elderly abdominal sepsis patients (age >65 years) had the following altered characteristics compared to nonelderly patient controls: lower mean arterial pressure, monocytes percentage, and red blood cell volume distribution width (p < 0.05); higher neutrophils percentage and neutrophils-to-lymphocytes ratio (p < 0.05); significantly increased monocyte-produced reactive oxygen (p < 0.05); increases neutrophilic secretion of TNF-α, as well as lower monocytic secretion of TNF-α (p < 0.05); higher neutrophil percentage (which was significantly higher in peripheral blood than monocyte percentage). Elderly patients also had significantly increased phagocytic activity in their neutrophils and monocytes (p < 0.05), significantly reduced neutrophils-produced reactive oxygen (p < 0.001), and significantly increased TNF-α secretion by monocytes and neutrophils (p < 0.05). We found that elderly patients have decreased immune cell function and increased release of cytokines compared to younger patients, suggesting individualized treatment plans targeting the elderly septic microenvironment could help prevent organ failure in elderly septic patients and improves patient survival.

Hematologic profiles and development of innate immune function in healthy Holstein calves during the pre-weaning period.

The development and state of innate immune cell function during the first 90 days of life in dairy calves have not been fully described. This transversal study attempted to examine the changes that occur in circulating blood cells and the innate immune response in healthy calves from birth to 89 days of age. Healthy Holstein calves represent three windows of development, G1 from 1 to 7 days old (n=26), G2 from 30 to 40 days old (n=28), and G3 from 60 to 89 days old (n=36) were sampled once each from a single herd. A few biomarkers of the general health and innate and inflammatory immune responses were measured. The youngest calves had the lowest red blood cell (RBC) counts, cell hemoglobin concentration means (CHCMs), red cell distribution widths (RDWs), and cell hemoglobin contents of mature red blood cells (CHm) compared with the other groups. They also had the lowest iron concentrations and highest intracellular myeloperoxidase indices. However, white blood cell (WBC) and lymphocyte concentrations gradually increased from G1 to G3. G2 calves had the lowest serum protein concentrations and highest number of innate immune cells compared with the other groups. Calves were able to mount phagocytic and ROS responses from birth. The physiologic responses of circulating blood cells and innate immune responses in dairy calves are shown according to age. Neonates had limitations in several RBC and WBC indices and immunologic responses that would likely impact overall vigor and health. Fortunately, these limitations resolve by 90 days of age.

NLRC3 expression in macrophage impairs glycolysis and host immune defense by modulating the NF-κB-NFAT5 complex during septic immunosuppression

Impairment of innate immune cell function and metabolism underlies immunosuppression in sepsis; however, a promising therapy to orchestrate this impairment is currently lacking. In this study, high levels of NOD-like receptor family CARD domain containing-3 (NLRC3) correlated with the glycolytic defects of monocytes/macrophages from septic patients and mice that developed immunosuppression. Myeloid-specific NLRC3 deletion improved macrophage glycolysis and sepsis-induced immunosuppression. Mechanistically, NLRC3 inhibits nuclear factor (NF)-κB p65 binding to nuclear factor of activated Tcells 5 (NFAT5), which further controls the expression of glycolytic genes and proinflammatory cytokines of immunosuppressive macrophages. This is achieved by decreasing NF-κB activation-co-induced by TNF-receptor-associated factor 6 (TRAF6) or mammalian target of rapamycin (mTOR)-and decreasing transcriptional co-activator p300 activity by inducing NLRC3 sequestration of mTOR and p300. Genetic inhibition of NLRC3 disrupted the NLRC3-mTOR-p300 complex and enhanced NF-κB binding to the NFAT5 promoter in concert with p300. Furthermore, intrapulmonary delivery of recombinant adeno-associated virus harboring a macrophage-specific NLRC3 deletion vector significantly improved the defense of septic mice that developed immunosuppression upon secondary intratracheal bacterial challenge. Collectively, these findings indicate that NLRC3 mediates critical aspects of innate immunity that contribute to an immunocompromised state during sepsis and identify potential therapeutic targets.

Innate lymphocytes: Role in alcohol-induced immune dysfunction.

Alcohol use is known to alter the function of both innate and adaptive immune cells, such as neutrophils, macrophages, B cells, and T cells. Immune dysfunction has been associated with alcohol-induced end-organ damage. The role of innate lymphocytes in alcohol-associated pathogenesis has become a focus of research, as liver-resident natural killer (NK) cells were found to play an important role in alcohol-associated liver damage pathogenesis. Innate lymphocytes play a critical role in immunity and homeostasis; they are necessary for an optimal host response against insults including infections and cancer. However, the role of innate lymphocytes, including NK cells, natural killer T (NKT) cells, mucosal associated invariant T (MAIT) cells, gamma delta T cells, and innate lymphoid cells (ILCs) type 1–3, remains ill-defined in the context of alcohol-induced end-organ damage. Innate-like B lymphocytes including marginal zone B cells and B-1 cells have also been identified; however, this review will address the effects of alcohol misuse on innate T lymphocytes, as well as the consequences of innate T-lymphocyte dysfunction on alcohol-induced tissue damage.

An activatable Mn(II) MRI probe for detecting peroxidase activity in vitro and in vivo

Myeloperoxidase (MPO), a hallmark of the function and activation of innate immune cells, can act as a ‘double-edged sword’, contributing to clear infection as well as causing tissue oxidizing damage in various inflammatory diseases. In this study, an activatable Mn(II) chelate-based magnetic resonance imaging (MRI) contrast agent (CA), Mn-TyEDTA (TyEDTA = tyrosine derived ethylenediaminetetraacetic acid) structurally featuring a phenol group as the electron-donor, was developed to sense the activity of peroxidase in vitro and in vivo. Mn-TyEDTA demonstrated a peroxidase activity-dependent relaxivity in the presence of horseradish peroxidase (HRP)/H2O2 with more than a 2.6-fold increase in water proton relaxivity produced (HRP, 500 U; H2O2, 4.5 eq). A mechanism of peroxidase-mediated Mn(II) monomer radical polymerization was confirmed with those oligomers of Mn-TyEDTA such as dimer, trimer and tetramer were found in the LC-MS study. Dynamic MR imaging of normal mice revealed rapid blood clearance and mixed renal and hepatobiliary elimination of Mn-TyEDTA. Furthermore, compared to liver-specific and non-specific extracellular contrast agents (Mn-BnO-TyEDTA (BnO-TyEDTA = benzyl tyrosine-derived ethylenediaminetetraacetic acid) and Gd-DTPA (DTPA = diethylene triamine penta-acetic acid)), MRI on a monosodium urate (MSU) crystal-induced acute mice model of arthritis showed that inflamed tissues could be selectively enhanced by Mn-TyEDTA, suggesting that this peroxidase-activatable Mn(II) MRI probe could potentially be used for noninvasive detection of MPO activity in vivo.

Hypoxia and hypoxia-inducible factor signals regulate the development, metabolism, and function of B cells.

Hypoxia is a common hallmark of healthy tissues in physiological states or chronically inflamed tissues in pathological states. Mammalian cells sense and adapt to hypoxia mainly through hypoxia-inducible factor (HIF) signaling. Many studies have shown that hypoxia and HIF signaling play an important regulatory role in development and function of innate immune cells and T cells, but their role in B cell biology is still controversial. B cells experience a complex life cycle (including hematopoietic stem cells, pro-B cells, pre-B cells, immature B cells, mature naïve B cells, activated B cells, plasma cells, and memory B cells), and the partial pressure of oxygen (PO2) in the corresponding developmental niche of stage-specific B cells is highly dynamic, which suggests that hypoxia and HIF signaling may play an indispensable role in B cell biology. Based on the fact that hypoxia niches exist in the B cell life cycle, this review focuses on recent discoveries about how hypoxia and HIF signaling regulate the development, metabolism, and function of B cells, to facilitate a deep understanding of the role of hypoxia in B cell-mediated adaptive immunity and to provide novel strategies for vaccine adjuvant research and the treatment of immunity-related or infectious diseases.

C3aR plays both sides in regulating resistance to bacterial infections.

Activation of the complement pathway results in the production of bioactive C3a, a product of C3 cleavage, which interacts with membrane-bound receptor C3aR to regulate innate immune cell function and outcome of bacterial infection. Specifically, previous research has identified mechanistically distinct and cell type–specific roles for C3aR in regulating innate immune cell inflammatory state, antimicrobial killing capacity, and metabolism. Historically, the production of C3a has been relegated to the serum; however, recent studies have provided evidence that various cell types can produce intracellular C3a that stimulates intracellular C3aR. In light of these new results, it is imperative that we revisit previous studies regarding the role of C3aR in controlling bacterial infections and analyze these results in the context of both extracellular and intracellular C3a production and C3aR activation. Thus, this review will cover specific roles of C3aR in driving cell type–specific and tissue specific responses during bacterial infections and emphasize the contribution of the C3a–C3aR axis in regulating host resistance to bacterial infection.

Store‐operated calcium entry controls innate and adaptive immune cell function in inflammatory bowel disease

Inflammatory bowel disease (IBD) is characterized by dysregulated intestinal immune responses. Using mass cytometry (CyTOF) to analyze the immune cell composition in the lamina propria (LP) of patients with ulcerative colitis (UC) and Crohn's disease (CD), we observed an enrichment of CD4+ effector T cells producing IL‐17A and TNF, CD8+ T cells producing IFNγ, T regulatory (Treg) cells, and innate lymphoid cells (ILC). The function of these immune cells is regulated by store‐operated Ca2+ entry (SOCE), which results from the opening of Ca2+ release‐activated Ca2+ (CRAC) channels formed by ORAI and STIM proteins. We observed that the pharmacologic inhibition of SOCE attenuated the production of proinflammatory cytokines including IL‐2, IL‐4, IL‐6, IL‐17A, TNF, and IFNγ by human colonic T cells and ILCs, reduced the production of IL‐6 by B cells and the production of IFNγ by myeloid cells, but had no effect on the viability, differentiation, and function of intestinal epithelial cells. T cell‐specific deletion of CRAC channel genes in mice showed that Orai1, Stim1, and Stim2‐deficient T cells have quantitatively distinct defects in SOCE, which correlate with gradually more pronounced impairment of cytokine production by Th1 and Th17 cells and the severity of IBD. Moreover, the pharmacologic inhibition of SOCE with a selective CRAC channel inhibitor attenuated IBD severity and colitogenic T cell function in mice. Our data indicate that SOCE inhibition may be a suitable new approach for the treatment of IBD.

Mitochondrial impairment and repair in the pathogenesis of systemic lupus erythematosus.

Nucleic acid autoantibodies, increase type I interferon (IFN-α) levels, and immune cell hyperactivation are hallmarks of systemic lupus erythematosus (SLE). Notably, immune cell activation requires high level of cellular energy that is predominately generated by the mitochondria. Mitochondrial reactive oxygen species (mROS), the byproduct of mitochondrial energy generation, serves as an essential mediator to control the activation and differentiation of cells and regulate the antigenicity of oxidized nucleoids within the mitochondria. Recently, clinical trials on normalization of mitochondrial redox imbalance by mROS scavengers and those investigating the recovery of defective mitophagy have provided novel insights into SLE prophylaxis and therapy. However, the precise mechanism underlying the role of oxidative stress-related mitochondrial molecules in skewing the cell fate at the molecular level remains unclear. This review outlines distinctive mitochondrial functions and pathways that are involved in immune responses and systematically delineates how mitochondrial dysfunction contributes to SLE pathogenesis. In addition, we provide a comprehensive overview of damaged mitochondrial function and impaired metabolic pathways in adaptive and innate immune cells and lupus-induced organ tissues. Furthermore, we summarize the potential of current mitochondria-targeting drugs for SLE treatment. Developing novel therapeutic approaches to regulate mitochondrial oxidative stress is a promising endeavor in the search for effective treatments for systemic autoimmune diseases, particularly SLE.

Evaluating the Phagocytic Index of Peripheral Leukocytes in Endometriosis by Plasma Experiments.

Background and Objectives: Endometriosis is a benign, chronic disease, that negatively influences the quality of life of affected women and is responsible for a remarkable amount of infertility. The pathophysiology of the disease is still not clarified, but the insufficient immune surveillance plays a significant role in it. The phagocyte function of innate immune cells may play a role in the elimination of ectopic endometrium. The purpose of this study is to examine the phagocyte function of neutrophil granulocytes and monocytes, incubated in heat-inactivated and not-inactivated plasma samples from healthy women and from women with endometriosis before and after the surgical treatment. Materials and Methods: Blood samples were collected from eight preoperative and eight postoperative patients with endometriosis before and after the surgical treatment, and from 16 healthy patients as controls. Neutrophil granulocytes, monocytes and blood plasma samples were isolated. Cells were incubated in different plasma samples, and the phagocytic index was determined with a fluorescence microscope. Results: The phagocytic index of granulocytes and monocytes isolated from patients with endometriosis was significantly decreased compared to healthy women after the cells were incubated in their own plasma. Preoperatively isolated cells from patients with endometriosis demonstrated an improved phagocyte function after incubating them in plasma samples from healthy controls. In contrast, the phagocytic activity of cells from healthy women significantly reduced after being incubated in the plasma of preoperative endometriosis patients. The heat-inactivation of plasma samples did not affect the results. Conclusions: Active endometriosis lesions may produce heat-stable systemic immunomodulatory factors, which reduced the phagocyte function of peripheral monocytes and neutrophil granulocytes. The phagocyte function of these cells can be normalized after the complete surgical removal of endometriosis, which then demonstrates similar values as in healthy women.

Effect of aging on monocyte phagocytic and inflammatory functions, and on the ex vivo inflammatory responses to lipopolysaccharide, in horses

Studies investigating age-related changes in the function of monocytes are currently limited for horses. Thus, the main goal of this study was to determine the effect of aging on monocyte phagocytic capacity and pro-inflammatory cytokine responses to bacterial lipopolysaccharide (LPS). A second goal of this work was to examine the effect of aging on the inflammatory cytokine responses to LPS in a whole blood ex vivo model. Seven healthy young adult (4–6 years of age) and seven healthy senior horses (>20 years of age) were enrolled. Phagocytosis of E. coli, and pro-inflammatory cytokine (TNFα) responses to LPS, were measured in monocytes by flow cytometry. Gene expressions of pro-inflammatory cytokines (TNFα, IL-1β, IL-6, IL-8, IL-18, CCL-5, CCL-2) were measured in peripheral blood mononuclear cells (PBMCs) and whole blood by RT-qPCR post incubation for 2 h or 6 h with a low (0.01 µg/mL) or a high (1 µg/mL) dose of LPS. Two sets of statistical models were applied to compare the age groups, one adjusted, and one unadjusted for the horses’ body condition scores (BCS). The percentage of monocytes that phagocytosed E. coli after 2 h of incubation was significantly lower in senior compared to young adult horses in the BCS-adjusted model. In the senior group, the expression of IL-1β in 2 h-0.01 µg/mL LPS-stimulated PBMCs was significantly higher than in the young adult group (BCS-adjusted and unadjusted models). In senior horses, expressions of IL-8 and IL-6 in whole blood samples stimulated for 6 h with 0.01 µg/mL LPS and for 2 h with 1 µg/mL LPS, respectively, were significantly lower than in young adult horses (BCS-adjusted models). The results of this study suggest that the phagocytic function of monocytes, as well as their IL-1β response to LPS may be altered in senior horses. In addition, the whole blood IL-8 and IL-6 gene expression responses to LPS may be insufficient in senior horses. While investigation of the effect of BCS on monocyte functions and whole blood pro-inflammatory LPS-responses was not a major goal of this work, it appears that adiposity may play a role in innate immune cell function, as significant differences between the age groups were often not apparent until the models were adjusted for BCS.

GM-CSF: A Double-Edged Sword in Cancer Immunotherapy.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine that drives the generation of myeloid cell subsets including neutrophils, monocytes, macrophages, and dendritic cells in response to stress, infections, and cancers. By modulating the functions of innate immune cells that serve as a bridge to activate adaptive immune responses, GM-CSF globally impacts host immune surveillance under pathologic conditions. As with other soluble mediators of immunity, too much or too little GM-CSF has been found to promote cancer aggressiveness. While too little GM-CSF prevents the appropriate production of innate immune cells and subsequent activation of adaptive anti-cancer immune responses, too much of GM-CSF can exhaust immune cells and promote cancer growth. The consequences of GM-CSF signaling in cancer progression are a function of the levels of GM-CSF, the cancer type, and the tumor microenvironment. In this review, we first discuss the secretion of GM-CSF, signaling downstream of the GM-CSF receptor, and GM-CSF’s role in modulating myeloid cell homeostasis. We then outline GM-CSF’s anti-tumorigenic and pro-tumorigenic effects both on the malignant cells and on the non-malignant immune and other cells in the tumor microenvironment. We provide examples of current clinical and preclinical strategies that harness GM-CSF’s anti-cancer potential while minimizing its deleterious effects. We describe the challenges in achieving the Goldilocks effect during administration of GM-CSF-based therapies to patients with cancer. Finally, we provide insights into how technologies that map the immune microenvironment spatially and temporally may be leveraged to intelligently harness GM-CSF for treatment of malignancies.

Cyclosporine A Regulates Influenza A Virus-induced Macrophages Polarization and Inflammatory Responses by Targeting Cyclophilin A.

Cyclosporine A (CsA) is an immunosuppressive drug that suppresses T cell responses and is broadly used in transplantation. Its immunosuppressive action is closely linked to its binding of cyclophilin A (CypA), which widely distributed in different cell types. CsA also regulates the functions of innate immune cells, but the mechanism remains elusive. Here, we investigate the role of CsA in regulating macrophages polarization in influenza A virus-infected mice and mouse bone marrow-derived macrophages. CsA downregulates pro-inflammatory cytokines expression and upregulates anti-inflammatory cytokines expression. Mechanically, CsA decreases the polarization of macrophages into pro-inflammatory M1 phenotype and increases the polarization of macrophages into anti-inflammatory M2 phenotype. Further studies show that CsA regulates macrophages polarization-associated IFN-γ/STAT1 and IL-4/STAT6 signaling pathways. Meanwhile, all these roles of CsA are eliminated when CypA is absent, suggesting that CsA regulates macrophages polarization and inflammatory responses depend on its binding to CypA. Collectively, these results reveal a crucial mechanism of CsA in attenuating IAV-induced inflammatory responses by a switch in macrophages polarization.

Deciphering Innate Immune Cell-Tumor Microenvironment Crosstalk at a Single-Cell Level.

The tumor microenvironment encompasses various innate immune cells which regulate tumor progression. Exploiting innate immune cells is a new frontier of cancer immunotherapy. However, the classical surface markers for cell-type classification cannot always well-conclude the phenotype, which will further hinge our understanding. The innate immune cells include dendritic cells, monocytes/macrophages, natural killer cells, and innate lymphoid cells. They play important roles in tumor growth and survival, in some cases promoting cancer, in other cases negating cancer. The precise characterization of innate immune cells at the single-cell level will boost the potential of cancer immunotherapy. With the development of single-cell RNA sequencing technology, the transcriptome of each cell in the tumor microenvironment can be dissected at a single-cell level, which paves a way for a better understanding of the cell type and its functions. Here, we summarize the subtypes and functions of innate immune cells in the tumor microenvironment based on recent literature on single-cell technology. We provide updates on recent achievements and prospects for how to exploit novel functions of tumor-associated innate immune cells and target them for cancer immunotherapy.

Helicobacter pylori and the Role of Lipopolysaccharide Variation in Innate Immune Evasion.

Helicobacter pylori is an important human pathogen that infects half the human population and can lead to significant clinical outcomes such as acute and chronic gastritis, duodenal ulcer, and gastric adenocarcinoma. To establish infection, H. pylori employs several mechanisms to overcome the innate and adaptive immune systems. H. pylori can modulate interleukin (IL) secretion and innate immune cell function by the action of several virulence factors such as VacA, CagA and the type IV secretion system. Additionally, H. pylori can modulate local dendritic cells (DC) negatively impacting the function of these cells, reducing the secretion of immune signaling molecules, and influencing the differentiation of CD4+ T helper cells causing a bias to Th1 type cells. Furthermore, the lipopolysaccharide (LPS) of H. pylori displays a high degree of phase variation and contains human blood group carbohydrate determinants such as the Lewis system antigens, which are proposed to be involved in molecular mimicry of the host. Lastly, the H. pylori group of outer membrane proteins such as BabA play an important role in attachment and interaction with host Lewis and other carbohydrate antigens. This review examines the various mechanisms that H. pylori utilises to evade the innate immune system as well as discussing how the structure of the H. pylori LPS plays a role in immune evasion.

Smoking-toxic substances and immunological consequences

Tobacco smoke is the leading cause of morbidity and mortality in modern times. The combustion products in tobacco smoke contain avariety of toxic substances. These substances have far-reaching effects on the immune system, altering both cell-mediated and humoral responses of the immune system. Hence, they affect the development, cytokine production, and effector function of both innate immune cells, including dendritic cells (DCs), macrophages, and natural killer (NK) cells, and adaptive immune cells, such as cytotoxic CD8+ Tcells, CD4+ Thcells, regulatory Tcells, and Bcells, resulting in proinflammatory responses and/or immune cell dysfunction. However, although tobacco products have been shown to impair humoral and cell-mediated immunity, neither the extent of this impairment nor its mechanisms are clearly understood.