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[This corrects the article DOI: 10.3389/fimmu.2026.1740323.].

Cutaneous leishmaniasis, caused by protozoan parasites of the Leishmania genus, remains a significant health concern in endemic regions such as the Middle-East, Asia, Latin America, and North Africa. The disease affects millions of people worldwide, with over one million new infections reported annually. Despite its health impact, there is currently no approved vaccine largely due to limited understanding of immunological mechanisms underlying protective immunity and disease pathogenesis. We previously reported that long pentraxin 3 (PTX3), a pattern recognition molecule involved in inflammation, tissue repair, and wound healing, is a negative regulator of immunity in primary Leishmania major infection. Specifically, we showed that PTX3 exacerbates disease by suppressing protective Th17 responses. Here, we extend these findings by showing that PTX3 also influences secondary (memory) immunity to L. major . PTX3 -deficient ( PTX3 -/- ) mice which had resolved a primary infection exhibited enhanced resistance to secondary challenge compared to their wild-type (WT) controls. This enhanced resistance correlated with higher frequencies of effector memory CD4 + T cells in the spleens and draining lymph nodes. Upon re-infection, healed PTX3 -/- mice produced significantly more IL-17A, while levels of IFN-γ, TNF-α, and IL-10 were similar. In vivo BrdU incorporation assays further revealed increased proliferation of IL-17 + CD4 + T cells in PTX3 -/- mice. Importantly, neutralization of IL-17A during secondary challenge abolished the enhanced resistance observed in PTX3 -/- mice, confirming a central role of IL-17 in PTX3-regulated secondary immunity. Collectively, our findings identify PTX3 as a key regulator of secondary immunity in cutaneous leishmaniasis and underscores the importance of IL-17 in this process.

C-reactive protein (CRP) is an evolutionarily conserved protein. From arthropods to humans, CRP has been found in every organism where the presence of CRP has been sought. Human CRP is a pentamer made up of five identical subunits which binds to phosphocholine (PCh) in a Ca -dependent manner. In various species, we define a protein as CRP if it has any two of the following three characteristics: First, it is a cyclic oligomer of almost identical subunits of molecular weight 20-30 kDa. Second, it binds to PCh in a Ca -dependent manner. Third, it exhibits immunological cross-reactivity with human CRP. In the arthropod horseshoe crab, CRP is a constitutively expressed protein, while in humans, CRP is an acute phase plasma protein and a component of the acute phase response. As the nature of CRP gene expression evolved from a constitutively expressed protein in arthropods to an acute phase protein in humans, the definition of CRP became distinctive. In humans, CRP can be distinguished from other homologous proteins such as serum amyloid P, but this is not the case for most other vertebrates and invertebrates. Literature indicates that the binding ability of CRP to PCh is less relevant than its binding to other ligands. Human CRP displays structure-based ligand-binding specificities, but it is not known if that is true for invertebrate CRP. During evolution, changes in the intrachain disulfide and interchain disulfide bonds and changes in the glycosylation status of CRP may be responsible for different structure-function relationships of CRP in various species. More studies of invertebrate CRP are needed to understand the reasons behind such evolution of CRP. Also, CRP evolved as a component of and along with the development of the immune system. It is important to understand the biology of ancient CRP molecules because the knowledge could be useful for immunodeficient individuals.

The innate immune system comprises a cellular and a humoral arm. Humoral pattern recognition molecules include complement components, collectins, ficolins, and pentraxins. These molecules are involved in innate immune responses by recognizing microbial moieties and damaged tissues, activating complement, exerting opsonic activity and facilitating phagocytosis, and regulating inflammation. The long pentraxin PTX3 is a prototypic humoral pattern recognition molecule that, in addition to providing defense against infectious agents, plays several functions in tissue repair and regulation of cancer-related inflammation. Characterization of the PTX3 molecular structure and biochemical properties, and insights into its interactome and multiple roles in tissue damage and remodeling support the view that microbial and matrix recognition are evolutionarily conserved functions of humoral innate immunity molecules.

Mucin1 (MUC1), a glycoprotein associated with an aggressive cancer phenotype and chemoresistance, is aberrantly overexpressed in a subset of clear cell renal cell carcinoma (ccRCC). Recent studies suggest that MUC1 plays a role in modulating cancer cell metabolism, but its role in regulating immunoflogosis in the tumor microenvironment remains poorly understood. In a previous study, we showed that pentraxin-3 (PTX3) can affect the immunoflogosis in the ccRCC microenvironment by activating the classical pathway of the complement system (C1q) and releasing proangiogenic factors (C3a, C5a). In this scenario, we evaluated the PTX3 expression and analyzed the potential role of complement system activation on tumor site and immune microenvironment modulation, stratifying samples in tumors with high (MUC1H) versus tumors with low MUC1 expression (MUC1L). We found that PTX3 tissue expression was significantly higher in MUC1H ccRCC. In addition, C1q deposition and the expressions of CD59, C3aR, and C5aR were extensively present in MUC1H ccRCC tissue samples and colocalized with PTX3. Finally, MUC1 expression was associated with an increased number of infiltrating mast cells, M2-macrophage, and IDO1+ cells, and a reduced number of CD8+ T cells. Taken together, our results suggest that expression of MUC1 can modulate the immunoflogosis in the ccRCC microenvironment by activating the classical pathway of the complement system and regulating the immune infiltrate, promoting an immune-silent microenvironment.

The humoral arm of innate immunity includes diverse molecules with antibody-like functions, some of which serve as disease severity biomarkers in coronavirus disease 2019 (COVID-19). The present study was designed to conduct a systematic investigation of the interaction of human humoral fluid-phase pattern recognition molecules (PRMs) with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Of 12 PRMs tested, the long pentraxin 3 (PTX3) and mannose-binding lectin (MBL) bound the viral nucleocapsid and spike proteins, respectively. MBL bound trimeric spike protein, including that of variants of concern (VoC), in a glycan-dependent manner and inhibited SARS-CoV-2 in three in vitro models. Moreover, after binding to spike protein, MBL activated the lectin pathway of complement activation. Based on retention of glycosylation sites and modeling, MBL was predicted to recognize the Omicron VoC. Genetic polymorphisms at the MBL2 locus were associated with disease severity. These results suggest that selected humoral fluid-phase PRMs can play an important role in resistance to, and pathogenesis of, COVID-19, a finding with translational implications.Stravalaci et al. examined recognition of SARS-CoV-2 by human soluble innate pattern recognition receptor. They report that pentraxin 3 and mannose-binding protein recognize viral nucleoprotein and spike, respectively. Mannose-binding lectin has antiviral activity, and human genetic polymorphisms of MBL2 are associated with more severe COVID-19.

The first line of defense in innate immunity is provided by cellular and humoral mediators. Pentraxins are a superfamily of phylogenetically conserved humoral mediators of innate immunity. PTX3, the first long pentraxin identified, is a soluble pattern recognition molecule rapidly produced by several cell types in response to primary pro-inflammatory signals and microbial recognition. PTX3 acts as an important mediator of innate immunity against pathogens of fungal, bacterial and viral origin, and as a regulator of inflammation, by modulating complement activation and cell extravasation, and facilitating pathogen recognition by myeloid cells. In sepsis, PTX3 plasma levels are associated with severity of the condition, patient survival, and response to therapy. In combination with other established biomarkers, PTX3 could improve stratification of sepsis patients and thus, complement the system of classification and monitoring of this disease.

Organoids are becoming particularly popular in modeling diseases that are difficult to reproduce in animals, due to anatomical differences in the structure of a given organ. Thus, they are a bridge between the in vitro and in vivo models. Human midbrain is one of the structures that is currently being intensively reproduced in organoids for modeling Parkinson’s disease (PD). Thanks to three-dimensional (3D) architecture and the use of induced pluripotent stem cells (iPSCs) differentiation into organoids, it has been possible to recapitulate a complicated network of dopaminergic neurons. In this work, we present the first organoid model for an idiopathic form of PD. iPSCs were generated from peripheral blood mononuclear cells of healthy volunteers and patients with the idiopathic form of PD by transduction with Sendai viral vector. iPSCs were differentiated into a large multicellular organoid-like structure. The mature organoids displayed expression of neuronal early and late markers. Interestingly, we observed statistical differences in the expression levels of LIM homeobox transcription factor alpha (early) and tyrosine hydroxylase (late) markers between organoids from PD patient and healthy volunteer. The obtained results show immense potential for the application of 3D human organoids in studying the neurodegenerative disease and modeling cellular interactions within the human brain.

Pentraxin 3 (PTX3) plays an important role in resistance to Aspergillus infections. Previous studies have suggested that PTX3 polymorphisms influence the risk of invasive aspergillosis among transplantation recipients. This study investigated the association between PTX3 gene polymorphisms and pulmonary aspergillosis in a chronic obstructive pulmonary disease (COPD) population. We included 173 consecutive inpatients with COPD. Thirty-six case patients were finally diagnosed with pulmonary aspergillosis. Among these, 25 case patients had invasive pulmonary aspergillosis (IPA), and 11 case patients had chronic pulmonary aspergillosis (CPA). Three single nucleotide polymorphisms (SNPs; rs2305619, rs3816527, and rs1840680) in the PTX3 gene were detected by polymerase chain reaction direct sequencing, and their associations with aspergillosis were evaluated. Plasma PTX3 levels were measured by enzyme-linked immunosorbent assay. Three SNPs were consistent with Hardy-Weinberg equilibrium. The recessive model for SNP rs1840680 suggests that the AA homozygote is associated with a higher risk for pulmonary aspergillosis (both IPA and CPA) in COPD patients. However, for genotypic and allele frequencies of rs2305619 and rs3816527, no association was observed. The distribution of haplotypes (rs2305619 and rs3816527) also showed no significant differences. Plasma PTX3 levels significantly increased in IPA patients. In the IPA group, the rs1840680 AA genotype subjects showed lower plasma PTX3 levels than those harboring AG and GG genotypes. This study showed a significant association between PTX3 rs1840680 polymorphisms and the susceptibility of pulmonary aspergillosis in patients with COPD. Plasma PTX3 levels may be potentially used as indicators for the diagnosis of IPA in COPD patients.

Introduction Pentraxin 3 (PTX3) is an essential regulator of the immune system. However, the immune‐modulatory role of PTX3 in the tumor microenvironment of glioma has not been elucidated. Methods The RNA seq samples were obtained from The Cancer Genome Atlas (TCGA) and the China Glioma Genome Atlas (CGGA) datasets. The single‐cell sequencing data of glioblastoma (GBM) samples were obtained from the Single Cell Portal platform (http://singlecell.broadinstitute.org). Immunohistochemistry was used to assess PTX3 expression, HAVCR2, PD‐1, PD‐L1, and CD276 in glioma sections from the Xiangya cohort (n = 60). Multiplex immunofluorescence staining of PTX3, CD68, and CD163 was performed in several solid cancer types, including GBM. HMC3 was cocultured with U251 and U87, and transwell assay and flow cytometry assay were performed to explore the migration and polarization activity of HMC3. Results PTX3 expression is significantly increased in GBM. PTX3 expression predicts worse survival in the Xiangya cohort. PTX3 is closely related to the expression of PD‐1, PD‐L1, CD276, and HAVCR2 in the tumor microenvironment. Additionally, PTX3 is involved in tumorigenic and immunogenic processes, especially the activity of macrophages based on various signaling pathways in cellular communications and critical transcription factors. Specifically, PTX3 actively mediates macrophages' infiltration, migration, and inflammation‐resolving‐polarization. PTX3 could also predict immunotherapy response. Conclusion PTX3 is critically involved in macrophage infiltration, migration, and inflammation‐resolving‐polarization and modulates an immunosuppressive microenvironment. In summary, we revealed the characteristics of PTX3 in the development of gliomas and the tumor immune microenvironment of cancer. The immunosuppressive property of PTX3 makes it a potential new therapeutic target and prognostic marker for the treatment of gliomas. Notably, PTX3 was found to mediate the infiltration, migration, and polarization of macrophages in GBM. Our study was expected to provide the background support for further in‐depth research about PTX3 in gliomas.