Biology subjects

Marcial-Juarez, E.

Publications and source records attributed to Marcial-Juarez, E..

5 recordsLinked to original sources

bioRxiv2025

Vaccine-induced antibodies are sufficient to limit Salmonella infection in the absence of complement or macrophages.

Antibodies to Salmonella Typhimurium (STm) can protect against infection. Understanding better how antibodies, complement, and leukocytes interplay can support vaccine development. We used an Outer Membrane Vesicle (OMV) vaccine against STm to study the in vivo function of anti-STm antibodies. Using intravital microscopy, we found that upon challenge, OMV-specific antibodies promote STm uptake by spleen and liver macrophages, with neutrophils rarely capturing the bacteria. Clodronate-liposome depletion of monocytic cells reveals that these cells help prevent antigen dissemination. After vaccination and challenge of C1q, C3, C4, and C5-deficient mice, all mice except C3-deficient were protected by OMV immunization. C3-deficient mice failed to mount significant germinal center and plasma cell responses; however, after the adoptive transfer of immune sera, they had lower bacterial burdens than controls. In vitro, we showed that antibodies enhance bacterial capture in macrophages. Thus, antibodies alone are sufficient to reduce bacterial burdens, but they cooperate with complement and macrophages to maximize their functions in vivo.

immunology↗

bioRxiv2024

Wild-type and single-O-antigen repeat outer-membrane vesicles induce equivalent protection against homologous and heterologous Salmonella challenge

Lipopolysaccharide O-antigen is an immunodominant target of protective antibodies. Variation in O-antigen structures limits antibody-mediated cross-protection between closely-related pathogens including Salmonella Typhimurium (STm) and S. Enteritidis (SEn). Bacterial outer membrane vesicles (OMV) are vaccine platforms presenting surface antigens in their natural conformations. To assess how O-antigen lengths impact antibody responses and control of homologous or heterologous infection, mice were immunized with STm-OMV containing wild-type O-antigen unit repeats (wt-OMV), [≤]1 O-antigen unit (wzy-OMV), or no O-antigen units (wbaP-OMV) respectively and challenged with either STm or SEn. Unexpectedly, anti-STm LPS IgG and protection to STm were comparable after immunization with either wt-OMV or wzy-OMV. Anti-porin responses were elevated after immunization with wzy-OMV and wbaP-OMV. A single immunization with any OMV induced minimal cross-protection against SEn, except in blood. In contrast, boosting with O-antigen-expressing OMV enhanced control of SEn infections by >10-fold. These results suggest that i) Antibody to single or variable-length O-antigen units are comparably protective against Salmonella; ii) Antigens other than immunodominant O-antigens may be targets of cross-reactive antibodies that moderate bacterial burdens; iii) Boosting can enhance the level of cross-protection against related Salmonella serovars and iv) High tissue burdens of Salmonella can be present in the absence of detectable bacteraemia.

immunology↗

bioRxiv2024

Discrete and conserved inflammatory signatures drive thrombosis in different organs after Salmonella infection

Inflammation-induced thrombosis is a common consequence of bacterial and viral infections, such as those caused by Salmonella Typhimurium (STm) and SARS-CoV-2. The identification of multi-organ thrombosis and the chronological differences in its induction and resolution raises significant challenges for successfully targeting multi-organ infection-associated thrombosis. Here, we identified specific pathways and effector cells driving thrombosis in the spleen and liver following STm infection. Thrombosis in the spleen is independent of IFN-{gamma} or the platelet C-type lectin-like receptor CLEC-2, while both molecules were previously identified as key drivers of thrombosis in the liver. Furthermore, we identified platelets, monocytes, and neutrophils as core constituents of thrombi in both organs. Depleting neutrophils or monocytic cells independently abrogated thrombus formation. Nevertheless, blocking TNF, which is expressed by both myeloid cell types, diminished both thrombosis and inflammation which correlates with reduced endothelial expression of E-selectin and leukocyte infiltration. Moreover, tissue factor and P-selectin glycoprotein ligand 1 inhibition impair thrombosis in both spleen and liver, identifying multiple common checkpoints to target multi-organ thrombosis. Therefore, organ-specific, and broad mechanisms driving thrombosis potentially allow tailored treatments based on the clinical need and to define the most adequate strategy to target both thrombosis and inflammation associated with systemic infections.

immunology↗

bioRxiv2023

Vi polysaccharide and conjugated vaccines afford similar early, IgM or IgG-independent control of infection but boosting with conjugated Vi vaccines sustains the efficacy of immune responses

Vaccination with Vi capsular polysaccharide (Vi-PS) or protein-Vi typhoid conjugate vaccine (TCV) can protect adults against Salmonella Typhi infections. TCVs offer better protection than Vi-PS in infants and may offer better protection in adults. Potential reasons for why TCV may be superior in adults are not fully understood. Here, we immunized wild-type (WT) mice and mice deficient in IgG or IgM with Vi-PS or TCVs (Vi conjugated to tetanus toxoid or CRM197) for up to seven months, with and without subsequent challenge with Vi-expressing Salmonella Typhimurium. Unexpectedly, IgM or IgG alone were similarly able to reduce bacterial burdens in tissues, and this was observed in response to conjugated or unconjugated Vi vaccines and was independent of antibody being of high affinity. Only in the longer-term after immunization (>5 months) were differences observed in tissue bacterial burdens of mice immunized with Vi-PS or TCV. These differences related to the maintenance of antibody responses at higher levels in mice boosted with TCV, with the rate of fall in IgG titres induced to Vi-PS being greater than for TCV. Therefore, Vi-specific IgM or IgG are independently capable of protecting from infection and any superior protection from vaccination with TCV in adults may relate to responses being able to persist better rather than from differences in the antibody isotypes induced. These findings suggest that enhancing our understanding of how responses to vaccines are maintained may inform on how to maximize protection afforded by conjugate vaccines against encapsulated pathogens such as S. Typhi.

immunology↗

bioRxiv2022

Salmonella infection induces the reorganisation of follicular dendritic cell networks concomitant with the failure to generate germinal centres

Germinal centres (GCs) are sites where plasma and memory B cells form to generate high-affinity, Ig class switched antibodies. Specialised stromal cells called follicular dendritic cells (FDCs) are essential for GC formation. During systemic Salmonella Typhimurium (STm) infection GCs are absent, whereas extensive extrafollicular switched antibody responses are maintained. The mechanisms that underpin the absence of GC formation are incompletely understood. Here, we show that STm-induces a reversible disruption of niches within the splenic microenvironment, including the T and B cell compartments and the marginal zone. Alongside to these effects post-infection, mature FDC networks are strikingly absent, whereas immature FDC precursors, including marginal sinus pre-FDCs (MadCAM-1+) and perivascular Pre-FDCs (PDGFR{beta}+) are enriched. As normal FDC networks re-establish, extensive GCs become detectable throughout the spleen. Therefore, the reorganisation of FDC networks and the loss of GC responses are key, parallel features of systemic STm infections. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=198 SRC="FIGDIR/small/519997v1_ufig1.gif" ALT="Figure 1"> View larger version (54K): org.highwire.dtl.DTLVardef@1917f1forg.highwire.dtl.DTLVardef@130ce0dorg.highwire.dtl.DTLVardef@127daf8org.highwire.dtl.DTLVardef@198d373_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗