Invasive fungal infections (IFIs) are a group of diseases caused by fungal pathogens, primarily Candida, Aspergillus, and Cryptococcus, which invade the body, proliferate in deep tissues, organs, or the bloodstream, and lead to localized or systemic severe infections. These infections impose significantclinical and economic burdens due to their high mortality rates, the high cost and limited availability of antifungal drugs, and the frequent adverse effects. Invasive fungal pathogens invade the host through hyphae, spores, and secreted adhesive proteins, primarily triggering disease via signal cascades resulting from the binding of fungal membrane ligands to host receptors, as well as through secreted substances and intrinsic toxins. Macrophages, as the first line of defense against invasive fungal pathogens, play a crucial role in combating IFIs. They combat fungal pathogens through mechanisms such as antigen recognition, phagocytosis, oxidative killing, polarization, and the regulation of various bioactive substances. This article reviews recent research progress on the mechanisms by which macrophages contribute to innate immunity against invasive fungal infections. Additionally, it discusses the immune evasion strategies employed by invasive fungal pathogens to counteract macrophages, aiming to provide new insights for the prevention and treatment of invasive fungal infections.
Humans ; Immunity, Innate ; Macrophages/immunology* ; Invasive Fungal Infections/microbiology* ; Animals ; Phagocytosis/immunology*

Asthma is a chronic inflammatory disease of the airway involving various cellular players. Among the different phenotypes of asthma, neutrophilic asthma is often associated with severe airway inflammation and a notable resistance to corticosteroid treatment. Macrophages, as innate immune cells, play a crucial role in the pathogenesis of neutrophilic asthma. They regulate neutrophil recruitment and activation to promote the progression of airway inflammation. During this process, macrophages also undergo changes in aspects such as efferocytosis. We reviewed the recent research progresses regarding the role of macrophages in the pathogenesis of neutrophilic asthma, aiming to provide valuable insights for future studies in this area.
Humans ; Asthma/pathology* ; Neutrophils/pathology* ; Macrophages/immunology* ; Animals ; Phagocytosis

To develop a method for determining the antibody-dependent cell-mediated phagocytosis (ADCP) activity of human epidermal growth factor receptor 2 (HER2)-targeted antibody drug conjugate (ADC) based on the reporter gene assay, we established an ADCP activity assay with Jurkat/NFAT/FcγRIIa cells as the effector cells and BT474 as the target cells. Then, the target cell density, the ratio of effector to target cells, the target cell adhesion time, the incubation time for drug administration, and the induction time after adding effector cells were optimized by the method of design of experiment (DOE). The method showed a significant dose-response relationship, which was complied with the four-parameter equation: y=(A-D)/[1+(x/C)^B]+D. The durability ranges of the target cell density, the ratio of effector to target cells, the target cell adhesion time, the incubation time for drug administration, and the induction time after adding effector cells were (2.5-4.0)×10⁵ cells/mL, 3-5, 1.0-2.0 h, 0 h, and 5.0-6.0 h, respectively. The results of the methodological validation showed that the linear equation was y=1.106 8x-0.011 6, r=0.969 2. The established method showed the relative accuracy ranging from -6.59% to 2.98% and the geometric coefficient of variation less than 11% in the intermediate precision test. Furthermore, the method was target-specific. The method was then applied to the determination of ADCP activity of HER2-targeted ADC, demonstrating the result of (103.5±5.7)%. We developed a reporter gene assay for determining the ADCP activity of HER2-targeted ADC and the assay demonstrated high accuracy and good reproducibility, which proposes a highly efficient and approache for evaluating ADCP effect of this HER2-targeted ADC, and also provides a referable technique for characterizing the Fc effector functions of ADCs with diverse targets.
Humans ; Receptor, ErbB-2/immunology* ; Phagocytosis/drug effects* ; Immunoconjugates/immunology* ; Genes, Reporter ; Antibody-Dependent Cell Cytotoxicity ; Jurkat Cells

Inhibition of macrophage-mediated phagocytosis has emerged as an essential mechanism for tumor immune evasion. One mechanism inhibiting the innate response is the presence of the macrophage inhibitory molecule, signal regulatory protein-α (SIRPα), on tumor-associated macrophages (TAMs) and its cognate ligand cluster of differentiation 47 (CD47) on tumor cells in the tumor microenvironment. On the basis of a recently discovered programmed death protein 1 (PD-1) in TAMs, we discuss the potential inhibitory receptors that possess new functions beyond T cell exhaustion in this review. As more and more immune receptors are found to be expressed on TAMs, the corresponding therapies may also stimulate macrophages for phagocytosis and thereby provide extra anti-tumor benefits in cancer therapy. Therefore, identification of biomarkers and combinatorial therapeutic strategies, have the potential to improve the efficacy and safety profiles of current immunotherapies.
Antigens, Surface ; metabolism ; Apoptosis Regulatory Proteins ; metabolism ; Humans ; Immunotherapy ; methods ; Macrophages ; immunology ; Neoplasms ; immunology ; pathology ; therapy ; Phagocytosis ; immunology ; Treatment Outcome ; Tumor Microenvironment ; immunology

No abstract available.
Asian Continental Ancestry Group/*genetics ; Base Sequence ; Bone Marrow Cells/cytology/pathology ; Cytomegalovirus Infections/diagnosis ; Epstein-Barr Virus Infections/diagnosis ; Female ; Flow Cytometry ; Heterozygote ; Humans ; Infant ; Killer Cells, Natural/cytology/immunology ; Lymphohistiocytosis, Hemophagocytic/*diagnosis/genetics ; Perforin/*genetics ; Phagocytosis ; Polymorphism, Single Nucleotide ; Republic of Korea ; Sequence Analysis, DNA

Lipooligosacharide (LOS) of Neisseria gonorrhoeae (gonococci, GC) is involved in the interaction of GC with host cells. Deletion of the alpha-oligosaccharide (alpha-OS) moiety of LOS (lgtF mutant) significantly impairs invasion of GC into epithelial cell lines. GC opacity (Opa) proteins, such as OpaI, mediate phagocytosis and stimulate chemiluminescence responses in neutrophils in part through interaction with members of the carcinoembryonic antigen (CEA) family, which includes CEACAM3 (CD66d), a human neutrophil specific receptor for phagocytosis of bacteria. In the present work, we examined the effects of OpaI-expressing lgtF mutant on phagocytosis by HeLa-CEACAM3 cells and chemiluminescence responses in neutrophils. The results showed that lgtF mutant even expressing OpaI completely lost the ability to promote either phagocytosis mediated by CEACAM3 interaction in HeLa cells or chemiluminescence responses in neutrophils. These data indicated that Opa proteins in the lgtF mutant, which might result from the conformational change, cannot be functional.
Antigens, Bacterial ; chemistry ; genetics ; immunology ; metabolism ; Carbohydrate Sequence ; Carcinoembryonic Antigen ; genetics ; immunology ; Gene Expression Regulation ; HeLa Cells ; Host-Pathogen Interactions ; Humans ; Lipopolysaccharides ; chemistry ; immunology ; Luminescent Measurements ; Mutation ; Neisseria gonorrhoeae ; genetics ; metabolism ; pathogenicity ; Neutrophils ; immunology ; microbiology ; Phagocytosis

Staphylococcus aureus is a major cause of hospital-acquired infection. Because the bacteria are very easy to become resistant to antibiotics, vaccination is a main method against S. aureus infection. Clumping factor B (ClfB) is an adhesion molecule essential for S. aureus to colonize in the host mucosa and is regarded as an important target antigen. In this study, we successfully used Escherichia coli to express a segment encoding the N1-N3 regions of ClfB protein (Truncated-ClfB) cloned from S. aureus. The protein was purified by affinity and ion exchange chromatographies and gel filtration. Rabbits were immunized three times with purified Truncated-ClfB. After that, blood was collected to prepare serum which were then used for measurement of antibody level. Phagocytosis of S. aureus opsonized by the serum was determined by a flow cytometry. Results show that the serum IgG titer reached 1:640 000. Phagocytosed S. aureus by polymorphonuclear leukocytes were significantly more when the bacteria were opsonized by the serum from Truncated-ClfB immunized rabbits than those from no immunized group (P < 0.01). Therefore, the results indicated that Truncated-ClfB could be a promising vaccine candidate against S. aureus infection.
Adhesins, Bacterial ; immunology ; Animals ; Antibodies, Bacterial ; blood ; Escherichia coli ; Flow Cytometry ; Immune Sera ; Immunoglobulin G ; blood ; Opsonin Proteins ; immunology ; Phagocytosis ; Rabbits ; Staphylococcal Infections ; immunology ; Staphylococcus aureus

Xiyanping is used to treat infectious diseases with antibiotics in clinic. The aim of this study is to investigate the mechanism of Xiyanping through studying the effect of the combination of Xiyanping with Cefazolin on the chemotaxis and phagocytic function of peripheral blood neutrophils in mice. Ten healthy mice were in control group. Forty healthy mice in experimental group were infected with staphylococcus aureus, and were randomly divided further into four groups, i. e. model group, Xiyanping group, Cefazolin group and combination group (Xiyanping with Cefazolin). Mice in the control group and model group were given normal saline (NS) through abdomen while those in other groups were given Xiyanping, Cefazolin, and Xiyanping with Cefazolin, respectively. The chemotaxis of peripheral blood neutrophils was detected with the transwell method, and the phagocytic function of peripheral blood neutrophils was analyzed with flow cytometry (FCM). In the present study, there was no significance on the chemotactic index of peripheral blood neutrophils in all the groups (P > 0.05). The actual phagocytotic rate and index of peripheral blood neutrophils in the blank group, Xiyanping group, and the combination group were significantly higher than those of the model group and Cefazolin group (P < 0.05). However, those were not significant in the blank group, Xiyanping group, and the combination group (P > 0.05) or between the model group and Cefazolin group (P> 0.05). Our results suggested the combination of Xiyanping and Cefazolin could enhance the therapeutic effect by improving the phagocytic function of peripheral blood neutrophils.
Animals ; Anti-Bacterial Agents ; pharmacology ; Cefazolin ; pharmacology ; Chemotaxis ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Mice ; Neutrophils ; cytology ; drug effects ; Phagocytosis ; Staphylococcal Infections ; immunology ; Staphylococcus aureus

Differentiated HL-60 is an effector cell widely used for the opsonophagocytic-killing assay (OPKA) to measure efficacy of pneumococcal vaccines. We investigated the correlation between phenotypic expression of immunoreceptors and phagocytic ability of HL-60 cells differentiated with N,N-dimethylformamide (DMF), all-trans retinoic acid (ATRA), or 1alpha, 25-dihydroxyvitamin D3 (VitD3) for 5 days. Phenotypic change was examined by flow cytometry with specific antibodies to CD11c, CD14, CD18, CD32, and CD64. Apoptosis was determined by flow cytometry using 7-aminoactinomycin D. Function was evaluated by a standard OPKA against serotype 19F and chemiluminescence-based respiratory burst assay. The expression of CD11c and CD14 gradually increased upon exposure to all three agents, while CD14 expression increased abruptly after VitD3. The expression of CD18, CD32, and CD64 increased during differentiation with all three agents. Apoptosis remained less than 10% until day 3 but increased after differentiation by DMF or ATRA. Differentiation with ATRA or VitD3 increased the respiratory burst after day 4. DMF differentiation showed a high OPKA titer at day 1 which sustained thereafter while ATRA or VitD3-differentiated cells gradually increased. Pearson analysis between the phenotypic changes and OPKA titers suggests that CD11c might be a useful differentiation marker for HL-60 cells for use in pneumococcal OPKA.
Antibodies, Bacterial/immunology ; Antigens, CD11c/metabolism ; Antigens, CD14/metabolism ; Antigens, CD18/metabolism ; Apoptosis/*immunology ; Biological Assay ; Cell Differentiation ; Cell Line, Tumor ; Cholecalciferol/pharmacology ; Dimethylformamide/pharmacology ; Flow Cytometry ; HL-60 Cells ; Humans ; Phagocytosis/*immunology ; Pneumococcal Vaccines/*immunology ; Receptors, IgG/metabolism ; Receptors, Immunologic/*biosynthesis ; Respiratory Burst/immunology ; Streptococcus pneumoniae/*immunology ; Tretinoin/pharmacology

Differentiated HL-60 is an effector cell widely used for the opsonophagocytic-killing assay (OPKA) to measure efficacy of pneumococcal vaccines. We investigated the correlation between phenotypic expression of immunoreceptors and phagocytic ability of HL-60 cells differentiated with N,N-dimethylformamide (DMF), all-trans retinoic acid (ATRA), or 1alpha, 25-dihydroxyvitamin D3 (VitD3) for 5 days. Phenotypic change was examined by flow cytometry with specific antibodies to CD11c, CD14, CD18, CD32, and CD64. Apoptosis was determined by flow cytometry using 7-aminoactinomycin D. Function was evaluated by a standard OPKA against serotype 19F and chemiluminescence-based respiratory burst assay. The expression of CD11c and CD14 gradually increased upon exposure to all three agents, while CD14 expression increased abruptly after VitD3. The expression of CD18, CD32, and CD64 increased during differentiation with all three agents. Apoptosis remained less than 10% until day 3 but increased after differentiation by DMF or ATRA. Differentiation with ATRA or VitD3 increased the respiratory burst after day 4. DMF differentiation showed a high OPKA titer at day 1 which sustained thereafter while ATRA or VitD3-differentiated cells gradually increased. Pearson analysis between the phenotypic changes and OPKA titers suggests that CD11c might be a useful differentiation marker for HL-60 cells for use in pneumococcal OPKA.
Antibodies, Bacterial/immunology ; Antigens, CD11c/metabolism ; Antigens, CD14/metabolism ; Antigens, CD18/metabolism ; Apoptosis/*immunology ; Biological Assay ; Cell Differentiation ; Cell Line, Tumor ; Cholecalciferol/pharmacology ; Dimethylformamide/pharmacology ; Flow Cytometry ; HL-60 Cells ; Humans ; Phagocytosis/*immunology ; Pneumococcal Vaccines/*immunology ; Receptors, IgG/metabolism ; Receptors, Immunologic/*biosynthesis ; Respiratory Burst/immunology ; Streptococcus pneumoniae/*immunology ; Tretinoin/pharmacology