Adjuvant conditioning enhances neutrophil function while inducing a suppressive peritoneal macrophage phenotype.

Adjuvants are widely used to boost the immune response during vaccination protocols. Our group has previously reported that repeated intraperitoneal administration of alum in mice, known as adjuvant conditioning (AC), creates an immunosuppressive environment that delays allogeneic graft rejection through NLRP3-dependent MDSC expansion. However, little is known about the effects of AC on the reprogramming of peritoneal cavity cells, particularly the different peritoneal macrophage populations, and the impact on the adaptive immune response.

Sustained early postnatal humoral and cellular immunity against human cytomegalovirus after transamniotic fetal mRNA vaccination in a rodent model.

Purpose: We sought to examine the humoral and cellular immune responses to transamniotic fetal mRNA vaccination against a human cytomegalovirus (hCMV) antigen over time in early postnatal life in a rodent model.

Methods: Seven pregnant Sprague Dawley dams underwent volume-matched intra-amniotic injections in all their fetuses (n = 82) of a custom-made mRNA encoding for hCMV envelope glycoprotein-B (hCMV-gB) antigen encapsulated by a lipid-polymer composite on gestational day 17 (E17; term = E21-22). At three time points between 1 and 3 months after birth, serum levels of antigen-specific hCMV-gB IgG antibodies were measured by ELISA.

Adjuvant conditioning shapes the adaptive immune response promoting immunotolerance via NLRP3/interleukin-1.

Although adjuvants typically enhance immune responses, we show that repeated alum administration-termed adjuvant conditioning (AC)-induces an immunosuppressive environment that delays allogeneic graft rejection by expanding myeloid-derived suppressor cells (MDSCs). AC-induced MDSCs suppress antigen-specific adaptive responses both and , a process dependent on NLRP3 and IL-1 signaling. Allogeneic pancreatic islets transplanted into AC-treated NLRP3 mice are not protected, confirming the necessity of NLRP3.

Targeting cargo to an unconventional secretory system within megakaryocytes allows the release of transgenic proteins from platelets.

Background: Platelets are essential for hemostasis and thrombosis and play vital roles during metastatic cancer progression and infection. Hallmarks of platelet function are activation, cytoskeletal rearrangements, and the degranulation of their cellular contents upon stimulation. While α-granules and dense granules are the most studied platelet secretory granules, the dense tubular system (DTS) also functions as a secretory system for vascular thiol isomerases.