Immunological Recognition Research Articles

Construction of Magnetic Core-Large Mesoporous Satellite Immunosensor for Long-Lasting Chemiluminescence and Highly Sensitive Tumor Marker Determination.

Chemiluminescence immunoassay exhibits high sensitivity and signal-to-noise ratio, thus attracting great attention in the early diagnosis and dynamic monitoring of diseases. However, the collection of conventional flash-type chemiluminescence signal (<5s) relies heavily on automatic sampling and reading instrument. Herein, a novel core-satellite multifunctional chemiluminescence immunosensor is designed for the efficient enrichment and highly sensitive determination of cancer biomarker carcinoembryonic antigen (CEA) with enhanced and long-lasting output signal that can be conveniently recorded by a simple microplate plate reading instrument. Anti-CEA monoclonal antibody 2 (Ab2) modified Fe3 O4 @SiO2 microspheres (Fe3 O4 @SiO2 -Ab2, 370nm in diameter) are synthesized as the core for selectively capturing and enriching target CEA in solution, and anti-human CEA monoclonal antibody 1 (Ab1) and horseradish peroxidase (HRP) co-immobilized dendritic large-mesoporous silica nanospheres (MSNs-HRP/Ab1, 80nm in diameter, pore size: 17nm) are synthesized as the satellite for efficient immunological recognition and signal amplification. The as-designed core-satellite magnetic chemiluminescence immunosensors exhibit a broad linear range of 0.01-20ngmL-1 and a low detection limit of 3.0pgmL-1 for the convenient, highly specific, and sensitive determination of CEA in human serum. Such core-satellite chemiluminescence immunosensors are expected to act as a powerful tool for in vitro detection of various biomarkers, overcome the defect of conventional chemiluminescence relying heavily on expensive and bulky automatic instruments and popularize chemiluminescence analysis to primary medical institutions and remote areas.

Engineered Collaborative Size Regulation and Shape Engineering of Tremella-Like Au-MnOx for Highly Sensitive Bimodal-Type Lateral Flow Immunoassays.

Engineered collaborative size regulation and shape engineering of multi-functional nanomaterials (NPs) offer extraordinary opportunities for improving the analysis performance. It is anticipated to address the difficulty in distinguishing color changes caused by subtle variations in target concentrations, thereby facilitating the highly sensitive analysis of lateral flow immunoassays (LFIAs). Herein, tremella-like gold-manganese oxide (Au-MnOx ) nanoparticles with precise MnCl2 regulation are synthesized as immuno signal tracers via a facile one-step redox reaction in alkaline condition at ambient temperature. Avail of the tunable elemental composition and anisotropy in morphology, black-colored tremella-like Au-MnOx exhibits superb colorimetric signal brightness, enhanced antibody coupling efficiency, marvelous photothermal performance, and unrestricted immunological recognition affinity, all of which facilitate highly sensitive multi-signal transduction patterns. In conjunction with the handheld thermal reader device, a bimodal-type LFIA that combines size-regulation- and shape-engineering-mediated colorimetric-photothermal dual-response assay (coined as the SSCPD assay) with a limit of detection of 0.012ngmL-1 for ractopamine (RAC) monitoring is achieved by integrating Au-MnOx with the competitive-type immunoreaction. This work illustrates the effectiveness of this strategy for establishing high-performance sensing, and the SSCPD assay may be extended to a wide spectrum of future point-of-care (POC) diagnostic applications.

Using patient-derived tumor organoids from common epithelial cancers to analyze personalized T-cell responses to neoantigens

Adoptive cell transfer of tumor-infiltrating lymphocytes (TIL) can mediate durable complete responses in some patients with common epithelial cancers but does so infrequently. A better understanding of T-cell responses to neoantigens and tumor-related immune evasion mechanisms requires having the autologous tumor as a reagent. We investigated the ability of patient-derived tumor organoids (PDTO) to fulfill this need and evaluated their utility as a tool for selecting T-cells for adoptive cell therapy. PDTO established from metastases from patients with colorectal, breast, pancreatic, bile duct, esophageal, lung, and kidney cancers underwent whole exomic sequencing (WES), to define mutations. Organoids were then evaluated for recognition by autologous TIL or T-cells transduced with cloned T-cell receptors recognizing defined neoantigens. PDTO were also used to identify and clone TCRs from TIL targeting private neoantigens and define those tumor-specific targets. PDTO were successfully established in 38/47 attempts. 75% were available within 2 months, a timeframe compatible with screening TIL for clinical administration. These lines exhibited good genetic fidelity with their parental tumors, especially for mutations with higher clonality. Immunologic recognition assays demonstrated instances of HLA allelic loss not found by pan-HLA immunohistochemistry and in some cases WES of fresh tumor. PDTO could also be used to show differences between TCRs recognizing the same antigen and to find and clone TCRs recognizing private neoantigens. PDTO can detect tumor-specific defects blocking T-cell recognition and may have a role as a selection tool for TCRs and TIL used in adoptive cell therapy.

Methionine oxidation selectively enhances T cell reactivity against a melanoma antigen

The impact of the peptide amino acids side-chain modifications on the immunological recognition has been scarcely explored. We investigate here the effect of methionine oxidation on the antigenicity of the melanoma immunodominant peptide 369-YMDGTMSQV-377 (YMD). Using CD8+ Tcell activation assays, we found that the antigenicity of the sulfoxide form is higher when compared to the YMD peptide. This is consistent with free energy computations performed on HLA-A∗02:01/YMD/TCR complex showing that this is lowered upon oxidation, paired with a steep increase in order at atomic level. Oxidized YMD forms were identified at the melanoma cell surface by LC-MS/MS analysis. These results demonstrate that methionine oxidation in the antigenic peptides may generate altered peptide ligands with increased antigenicity, and that this oxidation may occur invivo, opening up the possibility that high-affinity CD8+ Tcells might be naturally primed in the course of melanoma progression, as a result of immunosurveillance.

Assessment of the Biological Impact of SARS-CoV-2 Genetic Variation Using an Authentic Virus Neutralisation Assay with Convalescent Plasma, Vaccinee Sera, and Standard Reagents.

In the summer of 2020, it became clear that the genetic composition of SARS-CoV-2 was changing rapidly. This was highlighted by the rapid emergence of the D614G mutation at that time. In the autumn of 2020, the project entitled "Agility" was initiated with funding from the Coalition for Epidemic Preparedness Innovations (CEPI) to assess new variants of SARS-CoV-2. The project was designed to reach out and intercept swabs containing live variant viruses in order to generate highly characterised master and working stocks, and to assess the biological consequences of the rapid genetic changes using both in vitro and in vivo approaches. Since November 2020, a total of 21 variants have been acquired and tested against either a panel of convalescent sera from early in the pandemic, and/or a panel of plasma from triple-vaccinated participants. A pattern of continuous evolution of SARS-CoV-2 has been revealed. Sequential characterisation of the most globally significant variants available to us, generated in real-time, indicated that the most recent Omicron variants appear to have evolved in a manner that avoids immunological recognition by convalescent plasma from the era of the ancestral virus when analysed in an authentic virus neutralisation assay.

Combining Epigenetic and Immunotherapy in Cancer: Molecular Mechanisms

BACKGROUND: Immunotherapy, particularly the idea of immune checkpoint blockage is currently draw much attention in cancer treatment. It has been approved as an adjuvant, however, it cannot be a single cancer treatment.CONTENT: The discovery of the basic ligand-receptor interactions between immune and cancer cells inside the tumor microenvironment has led to the current interest in immunotherapy, specifically immune checkpoint inhibition. Different ligands produced by cancer cells interact with immune cells' surface receptors, activating inhibitory pathways, such programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1), that cause immune cells to become immunologically tolerant. On the other side, epigenetic modulators also play a critical role in enhancing the tumor microenvironment and regaining immunological recognition and immunogenicity. Some findings showed that such immune suppression can be reversed through various mechanisms involving antigens pathways, immune genetic, and epigenetic pathways. These findings have created a very encouraging foundation for research on the combination of epigenetic and immunotherapeutic drugs as cancer treatments.SUMMARY: The effectiveness of this suggested paradigm can only be demonstrated by clinical studies. Epigenetic treatment might replace immune checkpoint therapy as a powerful new cancer care technique that is generally well tolerated and should be proven with adequate clinical trials.KEYWORDS: epigenetics, immunotherapy, PTM, DNMT, HDAC, immune check point

Stability of Penicillin Determinant Reagents: Influence in Allergy Diagnostic Tests

Benzylpenicillin (BP) and its derivates have been used as determinants in allergy skin tests of β-lactam antibiotics (BLs), and covalently conjugated to poly-L-lysine in major determinants. The chemical stability of these compounds is related to their immunological recognition and the sensitivity of in vitro tests. The aim of this study was to analyse the stability of these determinants and the relationship between the modified chemical structure of determinants and specific IgE recognition.

Humanized CD36 (hCD36) mouse model supports the preclinical evaluation of therapeutic candidates targeting CD36.

CD36 (also known as scavenger receptor B2) is a multifunctional receptor that mediates lipid uptake, advanced oxidation protein products, and immunological recognition, and has roles in lipid accumulation, apoptosis, as well as in metastatic colonization in cancer. CD36 is involved in tumor immunity, metastatic invasion, and therapy resistance through various molecular mechanisms. Targeting CD36 has emerged as an effective strategy for tumor immunotherapy. In this study, we have successfully generated a novel hCD36 mouse (Unless otherwise stated, hCD36 mouse below refer to homozygous hCD36 mouse) strain where the sequences encoding the extracellular domains of the mouse Cd36 gene were replaced with the corresponding human sequences. The results showed that the hCD36 mice only expressed human CD36, and the proportion of each lymphocyte was not significantly changed compared with wild-type mice. Furthermore, CD36 monoclonal antibody could significantly inhibit tumor growth after treatment. Therefore, the hCD36 mouse represent a validated preclinical mouse model for the evaluation of tumor immunotherapy targeting CD36.

The First Three Decades of Gene Therapy

Gene therapy has fascinated clinicians, scientists, and patients since decades ago because of its potential to treat a disease at the genetic level. This can be achieved in many ways, including replacing a disease-causing gene with a healthy copy. Gene therapy must overcome complex tissue and cellular barriers to introduce genetic modifications into the nucleus of the target cells to drive a high level of gene expression. Moreover, the genetically corrected cells must be present in significantly large numbers in the body to reverse the diseased condition and yet able to escape immunological recognition and survive in the long term to sustain the benefit. This paper reviews the early work as well as recent developments in gene therapy, including improvements to viral vectors and novel treatment strategies, diseases targeted, approved gene therapies, and current challenges and prospects for future progress.

Mapping Polyclonal Antibody Responses to Infection Using Next-Generation Phage Display.

Peptide phage display has historically been used to epitope map monoclonal antibodies. More recently, by coupling this method with next-generation sequencing (so-called next-generation phage display, NGPD) to mass screen peptide binding events, the methodology has been successfully applied to map polyclonal antibody responses to infection. This leads to the identification of panels of mimotopes that represent the pathogen's epitopes. One potential advantage of using such an approach is that the mimotopes can represent not just linear epitopes but also conformational epitopes or those produced from post-translational modifications of proteins or from other non-protein macromolecules. The mapping of such complex immunological recognition of a pathogen can inform novel serological assay development and vaccine design. Here, we provide detailed methods for the application of NGPD to identify panels of mimotopes that are recognized specifically by antibodies from individuals with a particular infection.

Commercial Antivenoms Exert Broad Paraspecific Immunological Binding and In Vitro Inhibition of Medically Important Bothrops Pit Viper Venoms.

Snakebite envenoming is a life threatening neglected tropical disease that represents a considerable public health concern in the tropics. Viperid snakes of the genus Bothrops are among those of greatest medical importance in Latin America, and they frequently cause severe systemic haemotoxicity and local tissue destructive effects in human victims. Although snakebite antivenoms can be effective therapeutics, their efficacy is undermined by venom toxin variation among snake species. In this study we investigated the extent of paraspecific venom cross-reactivity exhibited by three distinct anti-Bothrops antivenoms (Soro antibotrópico-crotálico, BothroFav and PoliVal-ICP) against seven different Bothrops pit viper venoms from across Latin America. We applied a range of in vitro assays to assess the immunological binding and recognition of venom toxins by the antivenoms and their inhibitory activities against specific venom functionalities. Our findings demonstrated that, despite some variations, the monovalent antivenom BothroFav and the polyvalent antivenoms Soro antibotrópico-crotálico and PoliVap-ICP exhibited extensive immunological recognition of the distinct toxins found in the different Bothrops venoms, with Soro antibotrópico-crotálico generally outperformed by the other two products. In vitro functional assays revealed outcomes largely consistent with the immunological binding data, with PoliVap-ICP and BothroFav exhibiting the greatest inhibitory potencies against procoagulant and fibrinogen-depleting venom activities, though Soro antibotrópico-crotálico exhibited potent inhibition of venom metalloproteinase activities. Overall, our findings demonstrate broad levels of antivenom paraspecificity, with in vitro immunological binding and functional inhibition often highly comparable between venoms used to manufacture the antivenoms and those from related species, even in the case of the monovalent antivenom BothroFav. Our findings suggest that the current clinical utility of these antivenoms could possibly be expanded to other parts of Latin America that currently suffer from a lack of specific snakebite therapies.

Dual roles and potential applications of exosomes in HCV infections.

The hepatitis C virus (HCV) causes severe liver diseases, including hepatitis, liver cirrhosis, and hepatocellular carcinoma, which have high morbidity and mortality. Antibody targeting receptor-mediated HCV infections have limited therapeutic benefits, suggesting that the transmission of HCV infections is possibly mediated via receptor-independent mechanisms. Exosomes are membrane-enclosed vesicles with a diameter of 30-200 nm, which originate from the fusion of endosomal multivesicular bodies with the plasma membrane. Accumulating evidence suggests that exosomes have a pivotal role in HCV infections. Exosomes can transfer viral and cellular bioactive substances, including nucleic acids and proteins, to uninfected cells, thus spreading the infection by masking these materials from immunological recognition. In addition, exosomes originating from some cells can deliver antiviral molecules or prompt the immune response to inhibit HCV infection. Exosomes can be used for the diagnosis of HCV-related diseases, and are being presently evaluated as therapeutic tools for anti-HCV drug delivery. This review summarizes the current knowledge on the dual roles and potential clinical applications of exosomes in HCV infections.

Ultrasensitive plasmonic photothermal immunomagnetic bioassay using real-time and end-point dual-readout

One of the most straightforward and sensitive methods for combining the specificity of immunological recognition with the amplification capability of polymerase chain reaction (PCR) is the fluorescence-based immuno-PCR. But up until now, the majority of PCR-based immunoassays have utilized the pricey and lengthy Peltier-based heating technique. Herein, we introduce a plasmonic photothermal quantitative immuno-PCR (PPT-qiPCR) assay with real-time and end-point dual readout for biomarker detection using multifunctional plasmonic immunomagnetic nanoparticles (PIMNs). PPT-qiPCR is simple, time-saving and inexpensive compared with conventional iPCR platforms using PCR machine. We showed that an immunomagnetic technique utilizing PIMNs can shorten the time needed for collection, washing, and concentrating target proteins in the enzyme-linked immunosorbent assay (ELISA) procedure. Real-time readout also permits quick preliminary discrimination of target proteins with apparent sensitivity in commercial ELISA investigations. Additionally, in-situ end-point fluorescence or colorimetric detection using only the human eye considerably improve the assay sensitivity. Our PPT-qiPCR can significantly advance next-generation point-of-care molecular diagnostic technology and is anticipated to be immediately useful for the sensitive and quick identification of several disease biomarkers.

AuNPs@MoSe2 heterostructure as a highly efficient coreaction accelerator of electrocheluminescence for amplified immunosensing of DNA methylation

Electrocheluminescence analysis amplified by coreaction accelerators has experienced breakthrough in ultrasensitive detection of biomarkers. Herein, a highly efficient coreaction accelerator, two-dimensional layered MoSe2 nanosheets loaded with gold nanoparticles (AuNPs@MoSe2 heterostructure), is proposed to enhance the ECL efficiency of Ru(bpy)32+/tripropylamine (TPrA) system. The presence of AuNPs avoids the aggregation of MoSe2 nanosheets, and improves the electrical conductivity of modified surface. The AuNPs@MoSe2 modified electrode also provides a large area for loading of abundant capture probe. MoSe2 as an electroactive substrate can remarkably accelerate the generation of TPrA•+ radicals to react with electrooxidized Ru(bpy)32+, which achieves about 3.4-fold stronger ECL intensity. Thus, an enhanced ECL immunoassay method can be achieved after Ru(bpy)32+-doped silica nanoparticle labeled antibody (Ab2-Ru@SiO2) is captured to the modified electrode via immunological recognition. Using methylated DNA as a target, the immunosensor was prepared by binding capture DNA on AuNPs@MoSe2 modified electrode to successively capture the target, anti-5-methylcytosine antibody (anti-5mC) and Ab2-Ru@SiO2. The proposed strategy could detect 0.26 fM 5 mC (3σ) with a detectable concentration range of 1.0 fM - 10 nM at methylated DNA. This immunosensor showed excellent selectivity, good stability and reproducibility, and acceptable recovery, indicating the broad prospects of the novel coreaction accelerator in clinical diagnosis.

High-Throughput Analysis Reveals miRNA Upregulating α-2,6-Sialic Acid through Direct miRNA-mRNA Interactions.

Chemical biology has revealed the importance of sialic acids as a major signal in physiology and disease. The terminal modification α-2,6-sialic acid is controlled by the enzymes ST6GAL1 and ST6GAL2. Dysregulation of this glycan impacts immunological recognition and cancer development. microRNAs (miRNA, miR), noncoding RNAs that downregulate protein expression, are important regulators of glycosylation. Using our recently developed high-throughput fluorescence assay (miRFluR), we comprehensively mapped the miRNA regulatory landscape of α-2,6-sialyltransferases ST6GAL1 and ST6GAL2. We found, contrary to expectations, the majority of miRNAs upregulate ST6GAL1 and α-2,6-sialylation in a variety of cancer cells. In contrast, miRNAs that regulate ST6GAL2 were predominantly downregulatory. Mutational analysis identified direct binding sites in the 3'-untranslated region (UTR) responsible for upregulation, confirming it is a direct effect. The miRNA binding proteins AGO2 and FXR1 were required for upregulation. Our results upend common assumptions surrounding miRNA, arguing that upregulation by these noncoding RNA is common. Indeed, for some proteins, upregulation may be the dominant function of miRNA. Our work also suggests that upregulatory miRNAs enhance overexpression of ST6GAL1 and α-2,6-sialylation, providing another potential pathway to explain the dysregulation observed in cancer and other disease states.

Electrochemiluminescence nanoemitters for immunoassay of protein biomarkers

The family of electrochemiluminescent luminophores has witnessed quick development since the electrochemiluminescence (ECL) phenomenon of silicon nanoparticles was first reported in 2002. Moreover, these developed ECL nanoemitters have extensively been applied in sensitive detection of protein biomarker by combining with immunological recognition. This review firstly summarized the origin and development of various ECL nanoemitters including inorganic and organic nanomaterials, with an emphasis on metal-organic frameworks (MOFs)-based ECL nanoemitters. Several effective strategies to amplify the ECL response of nanoemitters and improve the sensitivity of immunosensing were discussed. The application of ECL nanoemitters in immunoassay of protein biomarkers for diagnosis of cancers and other diseases, especially lung cancer and heart diseases, was comprehensively presented. The recent development of ECL imaging with the nanoemitters as ECL tags for detection of multiplex protein biomarkers on single cell membrane also attracted attention. Finally, the future opportunities and challenges in the ECL biosensing field were highlighted.

A Au nanoparticle and polydopamine co-modified biosensor: A strategy for in situ and label-free surface plasmon resonance immunoassays

This article reports a surface plasmon resonance (SPR) strategy capable of label-free yet amplified in situ immunoassays for sensitive and specific detection of human IgG (hIgG), a serum marker that is important for the diagnosis of certain diseases. Primarily, a wavelength-modulated Kretschman configuration SPR analyzer was constructed, and Au film SPR biosensor chips were fabricated. Specifically, based on Au nanoparticles (AuNPs) adsorbed on the surface of the Au film, the AuNP/Au film was coated with polydopamine (PDA) to fix streptavidin (SA), and then the biotinylated antibodies were connected to the surface of the biosensor chip. The SPR analyzer was utilized for in situ real-time monitoring of hIgG. Due to the immunological recognition between the receptor and target, the surface plasmon waves produced by the attenuated total reflection were affected by the changes in the surface of the biosensor chip. The resonance wavelength ( λ R ) of the output spectra gradually redshifted, and the redshift degrees were directly related to the target concentration. The biosensor can realize the in situ detection of hIgG, displaying satisfactory sensitivity, excellent specificity and stability. Briefly, by monitoring the shift in λ R after specific binding, a new SPR immunoassay can be customized for label-free, in situ and amplified hIgG detection. The operating principle of this research could be extended as a common protocol for many other targets of interest.

Combination of oxaliplatin and POM-1 by nanoliposomes to reprogram the tumor immune microenvironment.

Some chemotherapy can damage tumor cells, releasing damage-related molecular patterns including ATP to improve immunological recognition against the tumor by immunogenic cell death (ICD). However, the immune-stimulating ATP may be rapidly degraded into immunosuppressive adenosine by highly expressed CD39 and CD73 in the tumor microenvironment, which leads to immune escape. Based on the above paradox, a liposome nanoplatform combined with ICD inducer (oxaliplatin) and CD39 inhibitor (POM-1) is designed for immunochemotherapy. The liposomes efficiently load the phospholipid-like oxaliplatin prodrug, and the cationic charged surface could adsorb POM-1. Rationally designed DSPE-PEGn-pep, on the one hand, could cover and hide POM-1 to avoid systematic toxicity and, on the other, achieve a response and charge reversal to favor POM-1 shedding and tumor deep penetration. This combination maximizes the ICD effect, and takes two-pronged advantage of stimulating the immune response and relieving immune suppression. The designed POL can effectively inhibit the growth of in situ, lung metastasis and postoperative recurrence melanoma model and form long-term immune memory. With the powerful clinical transformation potential of nanoliposome platforms, this new synergistic strategy is expected to enhance anticancer effects safely and effectively.

Switchable Multiplex Photoelectrochemical Immunoassay of Aβ42 and Aβ40 Based on a pH-Responsive i-Motif Probe and Pyrene-Based MOF Photocathode.

In accurately diagnosing Alzheimer's disease (AD) and distinguishing AD from other dementia, the concentration ratio of amyloid-beta 42 (Aβ42) to Aβ40 is more reliable than the concentration of Aβ42 alone. For the multiplex PEC assay, generating an independent photocurrent of multiple targets on a single interface is a great challenge. Herein, an i-motif-based switchable sensing approach is proposed to construct a pH-regulated multiplex PEC immunosensor for Aβ42 and Aβ40 by using Bi-TBAPy as an efficient photoactive cathode material. An independent photocurrent signal of Aβ42 and Aβ40 is produced through the regulation of the electron-transfer tunneling distance by a pH-dependent configuration transition of the i-motif DNA. In a 96-well plate, immunological recognition of Aβ42 (or Aβ40) coupled with an enzymatic catalytic reaction produces an acidic (or alkaline) lysis solution, which triggers the formation and unravelment of the i-motif structure. The above configuration transition regulates the distance between Au NPs labeled SH-DNA and Bi-TBAPy, leading to PEC signal switching. Smart integration of the pH-responsive switchable DNA probe with a high-efficiency photocathode enables the precise monitoring of Aβ42 and Aβ40 at a single interface in a wide detection range (10 fg/mL ∼ 1 μg/mL and 1 pg/mL ∼ 1 μg/mL) with detection limit of 4.5 fg/mL and 0.52 pg/mL, respectively. The proposed i-motif-based switchable sensing strategy paves a new avenue for a multiplex PEC assay on a single interface, showing great prospects in bioanalysis and early disease diagnosis.

The Influence of Antibiotic Resistance on Innate Immune Responses to Staphylococcus aureus Infection.

Staphylococcus aureus (S. aureus) causes a broad range of infections and is associated with significant morbidity and mortality. S. aureus produces a diverse range of cellular and extracellular factors responsible for its invasiveness and ability to resist immune attack. In recent years, increasing resistance to last-line anti-staphylococcal antibiotics daptomycin and vancomycin has been observed. Resistant strains of S. aureus are highly efficient in invading a variety of professional and nonprofessional phagocytes and are able to survive inside host cells. Eliciting immune protection against antibiotic-resistant S. aureus infection is a global challenge, requiring both innate and adaptive immune effector mechanisms. Dendritic cells (DC), which sit at the interface between innate and adaptive immune responses, are central to the induction of immune protection against S. aureus. However, it has been observed that S. aureus has the capacity to develop further antibiotic resistance and acquire increased resistance to immunological recognition by the innate immune system. In this article, we review the strategies utilised by S. aureus to circumvent antibiotic and innate immune responses, especially the interaction between S. aureus and DC, focusing on how this relationship is perturbed with the development of antibiotic resistance.