Research ArticleExperimental Studies
Open Access

Dysregulated Pro-inflammatory and Anti-inflammatory Cytokine Responses to Microbe-associated Molecular Patterns in X-linked Chronic Granulomatous Disease

NAOYA OMARU, TOMOHIRO WATANABE, AKANE HARA, MASAYUKI KURIMOTO, YASUHIRO MASUTA, YASUO OTSUKA, SHO MASAKI, KOSUKE MINAGA, KEN KAMATA, HAJIME HONJO, YASUYUKI ARAI, KOUHEI YAMASHITA and MASATOSHI KUDO
In Vivo July 2025, 39 (4) 1902-1911; DOI: https://doi.org/10.21873/invivo.13989

Abstract

Background/Aim: Chronic granulomatous disease (CGD) is a hereditary immune deficiency caused by mutations in nicotinamide adenine dinucleotide phosphate oxidase subunits. X-linked CGD caused by mutations in gp91phox is characterized by recurrent bacterial and fungal infections and by an increased incidence of autoimmunity and inflammatory bowel disease (IBD). The concurrent occurrence of microbial infection, autoimmunity, and IBD suggests the presence of complicated profiles of cytokines in patients with CGD. However, the pro-inflammatory and anti-inflammatory cytokine responses to microbe-associated molecular patterns (MAMPs) are poorly defined in patients with CGD.

Patients and Methods: We evaluated the cytokine and chemokine profiles in two patients with X-linked CGD. Peripheral blood mononuclear cells (PBMCs) were isolated and stimulated with various bacterial and fungal MAMPs.

Results: Production of C-X-C motif chemokine ligand 8, interleukin-6 (IL-6), IL-10, and tumor necrosis factor-α was enhanced by PBMCs isolated from patients with X-linked CGD as compared with those from healthy controls when stimulated with bacterial and fungal MAMPs.

Conclusion: A dysregulated balance between pro-inflammatory and anti-inflammatory cytokines may contribute to the manifestations of recurrent infection, autoimmunity, and IBD in patients with X-linked CGD.

Keywords:

Introduction

Chronic granulomatous disease (CGD) is an inherited immune deficiency disorder characterized by recurrent and life-threatening bacterial and fungal infections (1-4). Mutations in any of the five components of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase lead to the development of CGD (1-3). NADPH oxidase comprises five units: gp91phox (cytochrome b-245, beta polypeptide, CYBB), p22phox (cytochrome b-245, alpha polypeptide, CYBA), p47phox (neutrophil cytosolic factor 1, NCF1), p67phox (neutrophil cytosolic factor 2, NCF2), and p40phox (neutrophil cytosolic factor 4, NCF4) (1-3). Mutations in gp91phox and the other four enzyme units display X-linked and autosomal recessive inheritance (1-3, 5). NADPH oxidase is essential for eliminating intracellular pathogens because this enzyme unit is required for the production of superoxide anions and other reactive oxygen intermediates (ROIs) by neutrophils and antigen-presenting cells (APCs) (1-3). CGD mutations in gp91phox, p22phox, p47phox, p67phox, and p40phox are loss-of-function mutations leading to impaired pathogen removal due to markedly diminished production of superoxide and ROIs (1-3, 5). Thus, impaired production of superoxide and ROIs in the presence of CGD-associated mutations predispose individuals to bacterial and fungal infections (4).

Although CGD is characterized by recurrent infections and granuloma formation in various organs, patients with CGD often manifest autoimmune disorders (1, 6, 7). In particular, gastrointestinal (GI) complications including inflammatory bowel disease (IBD) occur in approximately 40-50% of patients with CGD bearing gp91phox or p47phox mutations (1, 8). More importantly, no association between residual ROI production and IBD occurrence has been reported (5). The mucosa of the GI tract is constantly exposed to bacterial and fungal microbe-associated molecular patterns (MAMPs); excessive pro-inflammatory cytokine responses against the intestinal microbiome and fungiome underlie the immunopathogenesis of IBD (9-13). Bacterial and fungal MAMPs are detected by pattern recognition receptors (PRRs) such as Toll-like receptors (TLRs), nucleotide-binding oligomerization domain 1 (NOD1), NOD2, and Dectin-1, all of which are expressed in the cytosol and membrane of APCs (9-13). A high incidence of IBD in patients with X-linked gp91phox CGD leads us to hypothesize that CGD-associated X-linked gp91phox mutations cause dysregulated cytokine responses upon recognition of MAMPs by PRRs.

Pro-inflammatory cytokine responses including interferon-γ (IFN-γ), interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) are counter-regulated by anti-inflammatory cytokines such as IL-10 and transforming growth factor-β1 (14-16). The excessive production of pro-inflammatory cytokines accompanied by diminished production of anti-inflammatory cytokines mediates host defense against invading pathogens, whereas such cytokine responses promote the development of autoimmunity (14-16). In contrast, a well-controlled balance between pro-inflammatory and anti-inflammatory cytokines contributes to the maintenance of immune homeostasis. Recurrent infections observed in patients with CGD may be explained by the decreased and increased production of pro-inflammatory and anti-inflammatory cytokines, respectively, upon MAMP exposure. In contrast, an increased pro-inflammatory cytokine production accompanied by decreased anti-inflammatory cytokine production may be involved in the development of autoimmunity in patients with CGD. Thus, the profiles of pro-inflammatory and anti-inflammatory cytokines produced by APCs upon recognition of MAMPs are likely to be more complicated than expected in patients with CGD. However, the pro-inflammatory and anti-inflammatory cytokine responses to MAMPs are poorly defined in patients with CGD.

This study aimed to determine the profiles of cytokines in responses to MAMPs in patients with X-linked CGD. Our findings show that peripheral blood mononuclear cells (PBMCs) isolated from patients with X-linked CGD caused by gp91phox mutations exhibit increased production of both pro-inflammatory and anti-inflammatory cytokines upon stimulation with MAMPs compared with healthy control (HC)-derived cells. The data presented here implicate the presence of complicated and dysregulated profiles of pro-inflammatory and anti-inflammatory cytokines in X-linked CGD.

Patients and Methods

Healthy controls (HCs) and patients with CGD. We studied the same HC cohorts (n=18) enrolled in a previous study (17). Two patients with CGD were enrolled in this study. Both cases were diagnosed with X-linked CGD bearing gp91phox mutations. The first case is a 44-year-old man with gp91phox deficiency due to a G-to-A point mutation at nucleotide 252 in exon 3. The second case is a 37-year-old man with gp91phox deficiency due to a G-to-A point mutation at nucleotide 389 in exon 10. Both patients had suffered from recurrent bacterial and fungal infections since infancy. The study protocol conformed to the ethical guidelines for human clinical research established by the Japanese Ministry of Health, Labor, and Welfare. This study was approved by the ethics committees of Kyoto University Hospital (approval No.: R-1574) and Kindai University Hospital (approval No.: 28-034). Written informed consent was obtained from all patients and HCs upon enrolment.

PBMC isolation and cell culture. PBMCs were isolated from HCs and patients as previously described (17). Briefly, blood withdrawn was centrifugated using Ficoll-Paque solution at 2,000 rpm for 20 min at room temperature and then the interface cells were collected. PBMCs were prepared after elimination of red blood cells by ACK-lysis solution. PBMCs (1×106 cells/ml) were cultured in RPMI-1640 medium containing 10% fetal bovine serum for seven days. Cells were stimulated with FK156 (20 μg/ml; Astellas Pharma, Tokyo, Japan), muramyl dipeptide (MDP, 20 μg/ml; InvivoGen, San Diego, CA, USA), PAM3CSK4 (PAM, 1 μg/ml; InvivoGen), lipopolysaccharide (LPS, 1 μg/ml; Sigma-Aldrich, St. Louis, MO, USA), zymosan (5 μg/ml, InvivoGen), curdlan (50 μg/ml, Sigma-Aldrich), heat-killed Candida albicans (HKCA, 1×108 cells/ml; InvivoGen), heat-killed Saccharomyces cerevisiae (HKSC, 1×108 cells/ml; InvivoGen), and monosodium urate crystals (MSU, 100 μg/ml; InvivoGen) as described previously (10, 12, 13, 17). The PRRs activated by ligands are summarized in Table I. Culture supernatants were obtained at 72 h and seven days for cytokine and immunoglobulin G (IgG) subclass assays, respectively. In our previous studies, we determined the concentrations of cytokines, chemokines, and IgG subclasses, all of which were produced by PBMCs isolated from 18 HCs upon exposure to MAMPs (17). In the present study, we compared the responses of cytokine, chemokine, and IgG subclasses induced by PBMCs isolated from patients with CGD against those from our established HC data. We also added data on responses of cytokines, chemokines, and IgG subclasses induced by PBMCs stimulated with heat-killed fungi (HKCA and HKSC) and MSU, one of the prototypical damage-associated molecular patterns (DAMPs, Table I) (18).

View this table:
Table I.

Summary of cytokine and chemokine responses to microbe-associated molecular patterns in patients with chronic granulomatous disease.

Enzyme-linked immunosorbent assays. Concentrations of cytokines and chemokines in the culture supernatants were determined using commercial enzyme-linked immunosorbent assay (ELISA) kits. Concentrations of C-X-C motif chemokine ligand 8 (CXCL8), IFN-γ, IL-1β, IL-6, IL-10, and TNF-α were measured using ELISA kits (eBioscience, San Diego, CA, USA) as previously described (19). Anti-human IgG1 and IgG4 antibodies (Abs; BD Biosciences, San Jose, CA, USA) were used as capture Abs and then horseradish peroxidase-labeled anti-human IgG Abs (BD Biosciences) were used as the detection Abs (17).

Statistical analyses. GraphPad Prism (GraphPad Software, San Diego, CA, USA) was used for all statistical analyses (13, 20). The Mann–Whitney U-test was used to evaluate the differences between groups. The Kruskal–Wallis test was used to evaluate the differences between multiple comparisons. For post-hoc analysis, the Bonferroni-corrected Mann–Whitney U-test was performed for comparison between groups. Effects were considered significant at p<0.05.

Results

Enhanced production of CXCL8, IL-6, and TNF-α by PBMCs from patients with CGD. We initially compared the production of pro-inflammatory cytokines and chemokines (CXCL8, IL-1β, IL-6, and TNF-α) by PBMCs between 18 HCs and two patients with X-linked CGD. CXCL8 production by HC-derived PBMCs was increased by stimulation with all of the MAMPs and DAMPs tested (Figure 1A). The PBMCs isolated from patients with X-linked CGD produced higher amounts of CXCL8, IL-6, and TNF-α upon stimulation with MDP (NOD2 ligand), LPS (TLR4 ligand), zymosan (TLR2 and Dectin-1 ligand), curdlan (Dectin-1 ligand), HKCA (Dectin-1 ligand), and HKSC (Dectin-1 ligand) than those produced by HC-derived PBMCs (Figure 1A, C and D, Table I). In contrast, no significant difference was observed in IL-1β production by PBMCs between HCs and patients with CGD. These data suggest that excessive production of pro-inflammatory cytokines, IL-6, and TNF-α in response to bacterial and fungal MAMPs underlie the immunopathogenesis of autoimmunity and IBD associated with X-linked CGD (Table I).

Figure 1.
Figure 1.

Production of cytokines and chemokines associated with innate immunity by peripheral blood mononuclear cells (PBMCs) isolated from healthy controls and patients with X-linked chronic granulomatous disease (CGD). PBMCs (1×106 cells/ml) isolated from healthy controls (n=14 or 12) and patients with X-linked CGD (n=2) were stimulated with FK156 (20 μg/ml), MDP (20 μg/ml), PAM (1 μg/ml), LPS (1 μg/ml), zymosan (5 μg/ml), curdlan (50 μg/ml), HKCA (1×108 cells/ml), HKSC (1×108 cells/ml), or MSU (100 μg/ml) for 72 h. Culture supernatants were subjected to enzyme-linked immunosorbent assay to measure (A) CXCL8, (B) IL-1β, (C) IL-6, and (D) TNF-α concentrations. Results are presented as the mean±standard error of mean. Each dot presents a value obtained from each subject. *p<0.05, **p<0.01, as compared with healthy control-derived PBMCs stimulated with each ligand. MDP: Muramyl dipeptide; PAM: PAM3CSK4; LPS: lipopolysaccharide; HKCA: heat-killed Candida albicans; HKSC: heat-killed Saccharomyces cerevisiae; MSU: monosodium urate crystals; CXCL8: C-X-C motif chemokine ligand 8; IL-1β: interleukin-1β; TNF-α: tumor necrosis factor-α.

Enhanced production of IL-10 by PBMCs from patients with CGD. We next evaluated the production of a prototypical Th1 cytokine (IFN-γ) and immunoregulatory cytokine (IL-10) by PBMCs from patients with CGD. IFN-γ production was variable, and no significant difference was observed in its production between HCs and patients with CGD (Figure 2A). Despite the increased production of pro-inflammatory IL-6 and TNF-α, IL-10 production by PBMCs from patients with CGD was markedly higher than in those derived from HCs upon stimulation with LPS, zymosan, and curdlan (Figure 2B). Thus, PBMCs from patients with X-linked CGD displayed enhanced pro-inflammatory and anti-inflammatory cytokine responses upon stimulation with bacterial and fungal MAMPs, suggesting the presence of a dysregulated balance between pro-inflammatory and anti-inflammatory cytokines (Table I).

Figure 2.
Figure 2.

Production of cytokines, IgG1, and IgG4 by peripheral blood mononuclear cells (PBMCs) isolated from healthy controls and patients with X-linked chronic granulomatous disease (CGD). PBMCs (1×106 cells/ml) isolated from healthy controls (n=18, 16, 14, or 12) and patients with X-linked CGD (n=2) were stimulated with FK156 (20 μg/ml), MDP (20 μg/ml), PAM (1 μg/ml), LPS (1 μg/ml), zymosan (5 μg/ml), curdlan (50 μg/ml), HKCA, 1×108 cells/ml), HKSC (1×108 cells/ml), or MSU (100 μg/ml) for 72 h or seven days. Culture supernatants were subjected to enzyme-linked immunosorbent assay to measure (A) IFN-γ, (B) IL-10, (C) IgG1, and (D) IgG4 concentrations. Results are presented as the mean±standard error of mean. Each dot presents a value obtained from each subject. *p<0.05, **p<0.01, compared with healthy control-derived PBMCs stimulated with each ligand. MDP: Muramyl dipeptide; PAM: PAM3CSK4; LPS: lipopolysaccharide; HKCA: heat-killed Candida albicans; HKSC: heat-killed Saccharomyces cerevisiae; MSU: monosodium urate crystals; IFN-γ: interferon-γ; IL-10: interleukin-10; IgG1: immunoglobulin G1; IgG4: immunoglobulin G4.

Enhanced production of IgG1 by PBMCs from patients with CGD. We finally measured the production of IgG1 and IgG4 by PBMCs. IgG1 is an immunostimulatory IgG subclass with the ability to form an immune complex and activate complements, whereas IgG4 is an immunosuppressive IgG subclass with a weak ability to form an immune complex and activate complements (21). IgG1 production, but not IgG4, was higher in PBMCs from patients with CGD than in cells derived from HCs, regardless of stimulation with or without MAMPs or DAMPs (Figure 2C and D). The enhanced IgG1 production by PBMCs from patients with CGD could be explained by recurrent bacterial and fungal infection episodes in both patients. Collectively, these analyses utilizing PBMCs clearly showed dysregulated pro-inflammatory and anti-inflammatory cytokine responses in patients with X-linked CGD.

Discussion

CGD is characterized by recurrent infections with bacteria and fungi, granuloma formation, and concurrent development of autoimmunity and IBD (1, 6, 7). The impaired production of superoxide anion and ROIs is considered responsible for the increased susceptibility to microbial infection in patients with CGD (1, 6, 7). Increased pro-inflammatory cytokine responses to MAMPs is considered beneficial for eliminating pathogens, whereas autoimmunity and IBD are caused by excessive pro-inflammatory cytokine responses triggered by MAMP activation of PRRs (15). In contrast, decreased anti-inflammatory cytokine responses mediate the development of autoimmunity and IBD (15). Thus, the increased susceptibility to microbial infection and the concurrent occurrence of autoimmunity and IBD, both of which are often observed in patients with CGD, cannot be explained by the increased and decreased pro-inflammatory cytokine responses accompanied by the decreased and increased anti-inflammatory cytokine responses, respectively. To address the pro-inflammatory and anti-inflammatory cytokine profiles in response to MAMPs in CGD, we recruited two patients with X-linked CGD caused by gp91phox mutations. In this study, we found that PBMCs isolated from patients with X-linked CGD produced large amounts of pro-inflammatory cytokines and chemokines (CXCL8, IL-6, and TNF-α) upon stimulation with bacterial and fungal MAMPs when compared with HC-derived cells. Notably, regulation of pro-inflammatory and anti-inflammatory cytokine responses was lost in patients with X-linked CGD. This may be explained by the enhanced IL-10 production by PBMCs isolated from patients with X-linked CGD upon stimulation with bacterial and fungal MAMPs compared with that in HC-derived cells. Collectively, the present study identified dysregulated pro-inflammatory and anti-inflammatory cytokine responses to bacterial and fungal MAMPs in patients with X-linked CGD. However, it should be noted that we measured cytokine and chemokine production in two patients with X-linked CGD. Therefore, these findings should be confirmed in further studies with a large number of patients with CGD, including X-linked and autosomal recessive types.

In line with the data presented here, Bylund et al. reported that PBMCs isolated from four patients with X-linked CGD exhibited enhanced IL-6 and TNF-α production upon stimulation with TLR2 and TLR4 ligands (22). Notably, we report several new findings in addition to those reported by Bylund et al. First, we evaluated the production of not only IL-6 and TNF-α but also of CXCL8, IL-1β, IFN-γ, and IL-10. Thus, we determined the profiles of pro-inflammatory and anti-inflammatory cytokines and chemokines. Second, we used fungal MAMPs as stimulators for PBMCs in addition to bacterial MAMPs. Therefore, we could evaluate pro-inflammatory and anti-inflammatory cytokine responses to a broad range of bacterial and fungal MAMPs.

Excessive production of CXCL8, IL-6, and TNF-α was observed in PBMCs isolated from patients with X-linked CGD upon exposure to bacterial and fungal MAMPs (Figure 1 and Table I). CXCL8 and TNF-α production by PBMCs stimulated with MSU, a prototypical DAMP, was comparable between HCs and patients with X-linked CGD. Thus, excessive production of pro-inflammatory chemokines and cytokines is specific to MAMP stimulation. Despite the enhanced pro-inflammatory cytokine responses to MAMPs, both patients with X-linked CGD had a history of recurrent bacterial and fungal infections. Therefore, the data presented in this study confirmed the hypothesis that diminished production of superoxide anion and ROIs due to defective NADPH activity is responsible for the increased susceptibility to microbial infection (1-3). Regarding the molecular mechanisms accounting for enhanced pro-inflammatory cytokine and chemokine responses in PBMCs from patients with X-linked CGD, the lack of ROI-mediated negative regulation of the secretion of pro-inflammatory mediators may be involved. Lekstrom-Himes et al. reported that ROIs induced by NADPH activation inhibit production of CXCL8, IL-1β, and IL-6 (23). Therefore, defective production of ROIs may be involved in the increased production of CXCL8 and IL-6 in patients with X-linked CGD.

Patients with X-linked CGD suffer from recurrent and life-threating bacterial and fungal infections (1-4). Fungal infections are considered a major determinant of survival in patients with X-linked CGD (4, 24). Enhanced production of IL-10, a prototypical immunosuppressive cytokine, may be involved in the repeated episodes of severe fungal infection. This is based on the observation that IL-10 production was considerably higher in PBMCs isolated from patients with X-linked CGD than in those from HCs upon exposure to two types of fungal cell wall components, zymosan and curdlan (Figure 2). Since zymosan and curdlan are recognized by cell-surface TLR2 and/or Dectin-1 expressed in APCs, TLR2 or Dectin-1-mediated IL-10 production likely contributed to the development of severe and complicated fungal infection in the two patients with X-linked CGD recruited in this study (10, 25).

LPS and MDP are unique bacterial cell wall components in that these MAMPs efficiently induce tolerogenic immune responses (26-28). Endotoxin tolerance is a phenomenon in which APCs initially stimulated with LPS exhibit diminished pro-inflammatory cytokine responses to LPS and other TLR ligands (26). In addition to LPS tolerance, initial exposure to MDP results in diminished pro-inflammatory cytokine responses induced by APCs upon stimulation with MDP as well as TLR ligands (27, 28). The two patients with X-linked CGD recruited in this study also experienced various bacterial infections, suggesting repeated systemic exposure to LPS and MDP. Despite repeated exposure to LPS and MDP, PBMCs isolated from the two patients displayed enhanced pro-inflammatory cytokine responses to bacterial MAMPs compared with those in HC-derived cells. The molecular mechanisms accounting for failure to induce MDP and LPS tolerance in patients with X-linked CGD remain unknown. In this regard, PBMCs from patients with X-linked CGD produce relatively large amounts of IL-6 and TNF-α upon stimulation with bacterial MAMPs via activation of nuclear factor-κB (NF-κB) (22). Induction of MDP or LPS tolerance is mediated by negative regulators of the TLR-NF-κB axis, IL-1 receptor-associated kinase-M (IRAK-M), and IFN regulatory factor 4 (IRF4) (26-28). Thus, impaired production of superoxide anion and ROIs due to defective NADPH activity may be involved in the failure to induce IRAK-M and/or IRF4 expression necessary for MDP and/or LPS tolerance.

GI tract complications, especially IBD, are frequently observed in patients with X-linked CGD. Excessive production of pro-inflammatory cytokines in response to bacterial and fungal MAMPs is associated with IBD development (9-13). The enhanced production of TNF-α and IL-6 observed in PBMCs from the two patients with X-linked CGD may be associated with the high incidence of IBD. However, the two patients have not been diagnosed with IBD until now. In this respect, PBMCs isolated from both patients displayed enhanced IL-10 production in response to bacterial and fungal MAMPs. Given that IL-10 is an immunoregulatory cytokine necessary for the maintenance of intestinal immune homeostasis, IBD development is likely to be inhibited by simultaneous induction of IL-10 in both cases (14). Alternatively, lack of IBD in both patients with X-linked CGD may be explained by the comparable levels of IL-1β. De Luca et al. reported that enhanced IL-1β production due to defective autophagy mediates the development of CGD-associated IBD and that the blockade of IL-1β-mediated signaling pathways ameliorates colitis in CGD (29).

In conclusion, we elucidated a part of the molecular mechanisms underlying the increased susceptibility to microbial infection and the development of autoimmunity and IBD in patients with X-linked CGD. The dysregulated pro-inflammatory and anti-inflammatory cytokine responses may underlie the increased susceptibility to microbial infection and development of autoimmunity and IBD. These findings should be confirmed in future studies addressing pro-inflammatory and anti-inflammatory cytokine responses in a large number of patients with CGD bearing various types of mutations.

Acknowledgements

The Authors thank Ms. Yukiko Ueno for her secretarial support.

Footnotes

  • Authors’ Contributions

    Conceptualization: Naoya Omaru, Tomohiro Watanabe, Kouhei Yamashita; Methodology: Naoya Omaru, Tomohiro Watanabe, Yasuyuki Arai, Kouhei Yamashita; Formal analysis and investigation: Naoya Omaru, Tomohiro Watanabe, Akane Hara, Masayuki Kurimoto, Yasuhiro Masuta, Yasuo Otsuka, Sho Masaki, Kosuke Minaga, Ken Kamata, Hajime Honjo, Kouhei Yamashita; Writing – original draft preparation: Naoya Omaru, Tomohiro Watanabe, Yasuyuki Arai, Kouhei Yamashita; Writing – review and editing: Naoya Omaru, Tomohiro Watanabe, Yasuyuki Arai, Kouhei Yamashita; Funding acquisition: Tomohiro Watanabe; Supervision: Masatoshi Kudo.

  • Conflicts of Interest

    The Authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this study.

  • Funding

    This work was supported by the 2025 Kindai University Research Enhancement Grant (KD2505) and the 2024 Kindai University Research Enhancement Grant (KD2405).

  • Artificial Intelligence (AI) Disclosure

    No artificial intelligence (AI) tools, including large language models or machine learning software, were used in the preparation, analysis, or presentation of this manuscript.

  • Received April 3, 2025.
  • Revision received April 21, 2025.
  • Accepted April 22, 2025.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).

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Dysregulated Pro-inflammatory and Anti-inflammatory Cytokine Responses to Microbe-associated Molecular Patterns in X-linked Chronic Granulomatous Disease
NAOYA OMARU, TOMOHIRO WATANABE, AKANE HARA, MASAYUKI KURIMOTO, YASUHIRO MASUTA, YASUO OTSUKA, SHO MASAKI, KOSUKE MINAGA, KEN KAMATA, HAJIME HONJO, YASUYUKI ARAI, KOUHEI YAMASHITA, MASATOSHI KUDO
In Vivo Jul 2025, 39 (4) 1902-1911; DOI: 10.21873/invivo.13989
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