Biology subjects

de Vries-Idema, J.

Publications and source records attributed to de Vries-Idema, J..

4 recordsLinked to original sources

bioRxiv2026

Polymorphonuclear neutrophils modulate the responses of human immune cells to vaccines in an in vitro blood cell culture system

Vaccine-induced immune responses are the result of an intricate interplay between different cell populations of the innate and adaptive immune system, which is so far only partly understood. In particular, the role of polymorphonuclear neutrophils (PMNs) has long been neglected. Here, we studied the effects of a whole inactivated virus influenza vaccine (WIV) in an in vitro system consisting of freshly isolated human PMNs alone or PMNs combined with autologous peripheral blood mononuclear cells (PBMCs). Isolated PMNs showed minimal responses to the vaccine with respect to apoptosis, gene expression, cytokine production, and reactive oxygen species production. However, in WIV-stimulated PMN/PBMC co-cultures, PMNs particularly enhanced monocyte dynamics, CD14-CD11c+ cell activation, effector T cell differentiation, and B cell antibody production. On the other hand, PMNs decreased T follicular helper cell frequencies. Without vaccine stimulation, PMN presence resulted in enhanced levels of baseline inflammatory cytokines in PMN/PBMC co-cultures. However, with vaccine stimulation, PMNs dampened the vaccine-induced cytokine secretion of PBMCs. These findings reveal PMNs as regulators of vaccine responses whose effects depend on crosstalk with other immune cells, balancing pro-inflammatory and adaptive immune activation. Author summaryPolymorphonuclear neutrophils (PMNs) are essential and predominant cells of the human innate immune system. Growing evidence implicates that PMNs are involved in vaccine-induced immune activation, but their exact role is so far poorly defined. In our study, human PMNs were tested alone to observe their response to whole inactivated virus influenza vaccine (WIV), or combined with autologous peripheral blood mononuclear cells (PBMCs) to investigate how their presence influences vaccine responses of various cell populations within PBMCs. Our results show that WIV had little direct effect on isolated PMNs. However, when PMNs were combined with other immune cells, PMNs acted as crucial regulators: they enhanced the activity of innate immune cells, regulated the responses to the vaccine of T and B cells, and helped control the overall level of inflammation. Our study forms the groundwork for a more comprehensive understanding of human immune cell interactions under vaccine stimulation.

immunology↗

bioRxiv2026

Immune-competent apical out airway organoids reveal distinct antiviral strategies of macrophages, neutrophils, and monocytes during influenza infection

The respiratory mucosa is the primary entry site for influenza virus and early antiviral immunity is governed there by interactions between epithelial cells and innate immune cells. However, mechanistic insight into these interactions in a human context is limited. Here, we established an immune-competent apical-out human airway organoid model that enables direct epithelial infection and controlled integration of innate immune cells. The organoids recapitulate key features of the human upper airway epithelium and support productive influenza virus replication. Using defined co-cultures, we uncovered distinct innate immune functions: macrophages suppress viral replication and restrict epithelial spread via production of type I and III interferons; neutrophils reduce extracellular virus levels without limiting epithelial infection, consistent with antiviral clearance mechanisms independent of interferon signaling; and monocytes exert modest, transient antiviral effects. Together, we use a human-relevant platform to define how distinct innate immune cells shape mucosal immunity at the respiratory epithelium, with direct implications for antiviral and vaccine development. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=171 SRC="FIGDIR/small/729766v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@612404org.highwire.dtl.DTLVardef@183aff0org.highwire.dtl.DTLVardef@93df5forg.highwire.dtl.DTLVardef@2de4a1_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗

bioRxiv2025

Respiratory viruses induce ferroptosis-like features in lung epithelial cells

During infection, viruses can modulate various regulated cell death (RCD) mechanisms to evade host immunity and enhance replication. However, less is known about how viruses alter the recently discovered RCD ferroptosis, which is characterized by an iron-dependent accumulation of lipid peroxidation and mitochondrial fragmentation. Influenza A virus (IAV) H1N1 and human adenovirus type C5 (HAdV-C5) are two common causes of respiratory infections of the upper and lower respiratory tract and can lead to severe illness. While IAV has been shown to induce ferroptosis to support its replication, less is known whether this is also true for HAdV-C5. Here we perform a comparative study investigating ferroptosis features during IAV H1N1 and HAdV-C5 infections using alveolar (A549) and bronchial (BEAS-2B) epithelial cells. Our data reveal that HAdV-C5, similar to H1N1, induces lipid peroxidation in a time-dependent manner, which is partially suppressed in the presence of the ferroptosis inhibitor ferrostatin-1 (Fer-1). Strikingly, HAdV-C5 infections do not lead to changes in ferritin protein levels, which is responsible for iron storage. Furthermore, both H1N1 and HAdV-C5 infections trigger a profound mitochondrial network remodeling, comparable to that induced by the ferroptosis inducer RSL3, with effects varying by cell type and infection stage. These findings suggest that HAdV-C5, just like H1N1, can activate ferroptosis-like processes, highlighting a potential role for lipid peroxidation and mitochondrial alterations in adenoviral pathogenesis. Understanding this mechanism may uncover new therapeutic targets for viral respiratory infections.

microbiology↗

bioRxiv2018

Cross-protective immune responses induced by sequential influenza virus infection and by sequential vaccination with inactivated influenza vaccines

Sequential infection with antigenically distinct influenza viruses induces cross-protective immune responses against heterologous virus strains in animal models. Here we investigated whether sequential immunization with antigenically distinct influenza vaccines can also provide cross-protection. To this end, we compared immune responses and protective potential against challenge with A(H1N1)pdm09 in mice infected sequentially with seasonal A(H1N1) virus followed by A(H3N2) virus or immunized sequentially with whole inactivated virus (WIV) or subunit (SU) vaccine derived from these viruses. Sequential infection provided solid cross-protection against A(H1N1)pdm09 infection while sequential vaccination with WIV, though not capable of preventing weight loss upon infection completely, protected the mice from reaching the humane endpoint. In contrast, sequential SU vaccination did not prevent rapid and extensive weight loss. Protection correlated with levels of cross-reactive but non-neutralizing antibodies of the IgG2a subclass, general increase of memory T cells and induction of influenza-specific CD4+ and CD8+ T cells. Adoptive serum transfer experiments revealed that despite lacking neutralizing activity, serum antibodies induced by sequential infection protected mice from weight loss and vigorous virus growth in the lungs upon A(H1N1)pdm09 virus challenge. Antibodies induced by WIV vaccination alleviated symptoms but could not control virus growth in the lung. Depletion of T cells prior to challenge revealed that CD8+ T cells, but not CD4+ T cells, contributed to cross-protection. These results imply that sequential immunization with WIV but not SU derived from antigenically distinct viruses could alleviate the severity of infection caused by a pandemic and may improve protection to unpredictable seasonal infection.\n\nImportanceNew influenza virus strains entering the human population may have large impact and therefore their emergence requires immediate action. Yet, since these strains are unpredictable, vaccines cannot be prepared in advance, at least not as long as there is no universal or broadly protective influenza vaccine available. It is therefore important to elucidate in how far immunization strategies based on currently available seasonal vaccines can provide at least some protection against newly emerging virus strains. Moreover, insight in the possible mechanisms of protection can guide the further development of pre-pandemic immunization strategies. Our study presents a vaccination strategy based on sequential administration of readily available seasonal whole inactivated virus vaccines which could be easily applied in case of a new pandemic. In addition, our study identifies immune mechanisms, in particular cross-reactive non-neutralizing antibodies and CD8+ T cells, which should be targeted by broadly protective influenza vaccines.

microbiology↗