Mechanisms Of Host Immune Response Research Articles

ZnO nanoparticles induced biofilm formation in Klebsiella pneumoniae and Staphylococcus aureus at sub-inhibitory concentrations.

Biofilm formation by the pathogenic bacteria generates a serious threat to the public health as it can increase the virulence potential, resistance to drugs, and escape from the host immune response mechanisms. Among the environmental factors that influence thebiofilm formation, there are only limited reports available on the role of antimicrobial agents. During the antimicrobial drug administration or application for any purpose, the microbial population can expect to get exposed to the sub-minimum inhibitory concentration (sub-MIC) of the drug which will have an unprecedented impact on microbial responses. Hence, the study has been conducted to investigate the effects of sub-MIC levels of zinc oxide nanoparticles (ZnO NPs) on the biofilm formation of Klebsiella pneumoniae and Staphylococcus aureus. Here, the selected bacteria were primarily screened for thebiofilm formation by using the Congo red agar method, and their susceptibility to ZnO NPs was also evaluated. Quantitative difference in biofilm formation by the selected organisms in the presence of ZnO NPs at the sub-MIC level was further carried out by using the microtiter plate-crystal violet assay. Further, the samples were subjected to atomic force microscopy (AFM) analysis to evaluate the properties and pattern of thebiofilm modulated under the experimental conditions used. From these, the organisms treated with sub-MIC levels of ZnO NPs were found to have enhanced biofilm formation when compared with the untreated sample. Also, no microbial growth could be observed for the samples treated with the minimum inhibitory concentration (MIC) of ZnO NPs. The results observed in the study provide key insights into the impact of nanomaterials on clinically important microorganisms which demands critical thinking on the antimicrobial use of nanomaterials.

The role of gut microbiota in host immune response mechanisms.

The role of gut microbiota in host immune response mechanisms.

Mycobacterium tuberculosis: immune response, biomarkers, and therapeutic intervention.

Although tuberculosis (TB) is an infectious disease, the progression of the disease following Mycobacterium tuberculosis (MTB) infection is closely associated with the host's immune response. In this review, a comprehensive analysis of TB prevention, diagnosis, and treatment was conducted from an immunological perspective. First, we delved into the host's immune response mechanisms against MTB infection as well as the immune evasion mechanisms of the bacteria. Addressing the challenges currently faced in TB diagnosis and treatment, we also emphasized the importance of protein, genetic, and immunological biomarkers, aiming to provide new insights for early and personalized diagnosis and treatment of TB. Building upon this foundation, we further discussed intervention strategies involving chemical and immunological treatments for the increasingly critical issue of drug-resistant TB and other forms of TB. Finally, we summarized TB prevention, diagnosis, and treatment challenges and put forward future perspectives. Overall, these findings provide valuable insights into the immunological aspects of TB and offer new directions toward achieving the WHO's goal of eradicating TB by 2035.

Comparative spatial transcriptomic profiling of severe acute respiratory syndrome coronavirus 2 Delta and Omicron variants infections in the lungs of cynomolgus macaques.

Recently emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variants are generally less pathogenic than previous strains. However, elucidating the molecular basis for pulmonary immune response alterations is challenging owing to the virus's heterogeneous distribution within complex tissue structure. Here, we revealed the spatial transcriptomic profiles of pulmonary microstructures at the SARS-CoV-2 infection site in the nine cynomolgus macaques upon inoculation with the Delta and Omicron variants. Delta- and Omicron-infected lungs had upregulation of genes involved in inflammation, cytokine response, complement, cell damage, proliferation, and differentiation pathways. Depending on the tissue microstructures (alveoli, bronchioles, and blood vessels), there were differences in the types of significantly upregulated genes in each pathway. Notably, a limited number of genes involved in cytokine and cell damage response were differentially expressed between bronchioles of the Delta- and Omicron-infection groups. These results indicated that despite a significant antigenic shift in SARS-CoV-2, the host immune response mechanisms induced by the variants were relatively consistent, with limited transcriptional alterations observed only in large airways. This study may aid in understanding the pathogenesis of SARS-CoV-2 and developing a clinical strategy for addressing immune dysregulation by identifying potential transcriptional biomarkers within pulmonary microstructures during infection with emerging variants.

Human ascariasis, an evolutionary complex relationship between host and parasite

La ascariasis es una enfermedad parasitaria que diezma la salud de cientos de miles de seres humanos, especialmente en los países en desarrollo. Sin embargo, la falta de profilaxis adecuada del parásito, asociado con un mayor riesgo de sufrir enfermedades inmunes, es un problema principalmente en los países desarrollados donde la prevalencia del parásito es muy baja. La relación evolutiva y los mecanismos por los cuales el parásito fue capaz de colonizar y establecerse en el huésped humano aún no se han descifrado. Del mismo modo, los mecanismos inmunes (proximales) de respuesta del huésped para eliminar o controlar el parásito no se entienden completamente. La comprensión de estos mecanismos nos permitirá establecer mejores tratamientos médicos, evitando efectos indeseables y más enfocados en el control de la parasitosis, así como para la terapia de estas enfermedades inmunológicas asociadas con la relación huésped-ascárido.

Skin Microbiota in Atopic Dermatitis.

The skin microbiota represents an ecosystem composed of numerous microbial species interacting with each other, as well as with host epithelial and immune cells. The microbiota provides health benefits to the host by supporting essential functions of the skin and inhibiting colonization with pathogens. However, the disturbance of the microbial balance can result in dysbiosis and promote skin diseases, such as atopic dermatitis (AD). This review provides a current overview of the skin microbiota involvement in AD and its complex interplay with host immune response mechanisms, as well as novel therapeutic strategies for treating AD focused on restoring skin microbial homeostasis.

Immunity and Therapeutic Approaches against Coronavirus Disease 2019

The Coronavirus disease 19 (COVID-19) pandemic has resulted in considerable mortality and morbidity worldwide since identified in Wuhan in late 2019. It was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), which is a causative agent of human respiratory tract infection. The detailed mechanism of host immune response and pathogenesis to this virus is not fully elucidated. In this review, we recapitulate the characteristics of immune pathogenies of SARS-CoV-2 infection based on t

Transcriptome Analysis of Host Inflammatory Responses to the Ectoparasitic Mite Sarcoptes scabiei var. hominis.

Scabies, a human skin infestation caused by the ectoparasitic mite Sarcoptes scabiei var. hominis, affects more than 200 million people globally. The prevailing knowledge of the disease process and host immune response mechanisms is limited. A better understanding of the host-parasite relationship is essential for the identification of novel vaccine and drug targets. Here we aimed to interrogate the transcriptomic profiles of mite-infested human skin biopsies with clinical manifestations of ordinary scabies subjects (“OS”; n = 05) and subjects naive to scabies (“control”; n = 03) using RNASeq data analysis. A combined clustering, network, and pathway mapping approach enabled us to identify key signaling events in the host immune and pro-inflammatory responses to S. scabiei infestation. The clustering patterns showed various differentially expressed genes including inflammatory responses and innate immunity genes (DEFB4A, IL-19, CXCL8, CSF3, SERPINB4, S100A7A, HRNR) and notably upregulation of the JAK-STAT pathway in scabies-infested samples. Mite-infested human skin biopsies (GSE178563) were compared with an ex-vivo porcine infested model (E-MTAB-6433) and human skin equivalents (GSE48459). Marked enrichment of immune response pathways (JAK-STAT signaling, IL-4 and IL-13 pathway, and Toll receptor cascade), chemokine ligands and receptors (CCL17, CCL18, CCL3L1, CCL3L3, CCR7), and cytokines (IL-13 and IL-20) were observed. Additionally, genes known for their role in psoriasis and atopic dermatitis were upregulated, e.g., IL-19. The detailed transcriptomic profile has provided an insight into molecular functions, biological processes, and immunological responses and increased our understanding about transcriptomic regulation of scabies in human.

Characterisation and comparison of immune response mechanisms in an indigenous and a commercial pig breed after classical swine fever vaccination.

The live attenuated classical swine fever (CSF) vaccine has been successfully used to prevent and control CSF outbreaks for 6 decades. However, the immune response mechanisms against the vaccine remain poorly understood. Moreover, very few reports exist regarding the breed differences in the response to CSF vaccine. In this study, we generated the peripheral blood mononuclear cell transcriptomes of indigenous Ghurrah and commercial Landrace pig breeds, before and 7 days after CSF vaccination. Subsequently, between and within-breed differential gene expression analyses were carried out. Results revealed large differences in pre-vaccination peripheral blood mononuclear cell transcriptome profiles of the two breeds, which were homogenised 7 days after vaccination. Before vaccination, gene set enrichment analysis showed that pathways related to antigen sensing and innate immune response were enriched in Ghurrah, while pathways related to adaptive immunity were enriched in Landrace. Ghurrah exhibited greater immunomodulation compared to Landrace following the vaccination. In Ghurrah, cell-cycle processes and T-cell response pathways were upregulated after vaccination. However, no pathways were upregulated in Landrace after vaccination. Pathways related to inflammation were downregulated in both the breeds after vaccination. Key regulators of inflammation such as IL1A, IL1B, NFKBIA and TNF genes were strongly downregulated in both the breeds after vaccination. Overall, our results have elucidated the mechanisms of host immune response against CSF vaccination in two distinct breeds and revealed common key genes instrumental in the global immune response to the vaccine.

Biomarkers and Immune Repertoire Metrics Identified by Peripheral Blood Transcriptomic Sequencing Reveal the Pathogenesis of COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global crisis; however, our current understanding of the host immune response to SARS-CoV-2 infection remains limited. Herein, we performed RNA sequencing using peripheral blood from acute and convalescent patients and interrogated the dynamic changes of adaptive immune response to SARS-CoV-2 infection over time. Our results revealed numerous alterations in these cohorts in terms of gene expression profiles and the features of immune repertoire. Moreover, a machine learning method was developed and resulted in the identification of five independent biomarkers and a collection of biomarkers that could accurately differentiate and predict the development of COVID-19. Interestingly, the increased expression of one of these biomarkers, UCHL1, a molecule related to nervous system damage, was associated with the clustering of severe symptoms. Importantly, analyses on immune repertoire metrics revealed the distinct kinetics of T-cell and B-cell responses to SARS-CoV-2 infection, with B-cell response plateaued in the acute phase and declined thereafter, whereas T-cell response can be maintained for up to 6 months post-infection onset and T-cell clonality was positively correlated with the serum level of anti-SARS-CoV-2 IgG. Together, the significantly altered genes or biomarkers, as well as the abnormally high levels of B-cell response in acute infection, may contribute to the pathogenesis of COVID-19 through mediating inflammation and immune responses, whereas prolonged T-cell response in the convalescents might help these patients in preventing reinfection. Thus, our findings could provide insight into the underlying molecular mechanism of host immune response to COVID-19 and facilitate the development of novel therapeutic strategies and effective vaccines.

Severe acute respiratory syndrome Coronavirus-2 infection: A synopsis of the host immune responses and viral immune evasion strategies involved

The novel coronavirus designated as SARS-CoV-2 is the etiological agent of coronavirus disease 2019 (COVID-19), which rendered the care of the global health powerless and plunged the world economy into a historic decline. This disease is characterized by different clinical pictures; ranging from asymptomatic mild phase to severe illness with acute respiratory distress syndrome (ARDS), in addition to having no specific therapy. The protective immunity involving solid CD4+ T-cells, viral specific CD8+ T-cells and the neutralizing immunoglobulins have been established in most of the convalescent COVID-19 individuals. On the other hand, the host immune response to severe COVID-19 infection has been attributed to the inflammatory cytokine storm, and to influx of the activated immune cells to the lungs; leading to severe pneumonia, extensive ARDS and finally to death. Despite of this, the protective and pathogenic aspects of the human immunity have not been fully elucidated. Recent attempts conducted by several published research works have focused on information derived from the immune responses to the severe acute respiratory syndrome-related coronavirus diseases (mainly; SARS and MERS). However, these works lack sufficiency due to variations in the transmissibility, virulence, host-virus interactions and the immune evasion mechanisms. Hence, adequate understanding of the host immune response mechanisms to SARS-CoV-2 will generate the impetus towards effective control and preventive measures. The objectives of this article were to provide an overview of the host immune responses to SARS-CoV-2 infection, the viral immune evasion strategies, and to define certain knowledge gaps that require further studies.

Targeting Salmonella Typhimurium Invasion and Intracellular Survival Using Pyrogallol.

Salmonella enterica serovar Typhimurium, an intracellular pathogen, evades the host immune response mechanisms to cause gastroenteritis in animals and humans. After invading the host cells, the bacteria proliferate in Salmonella-containing vacuole (SCV) and escapes from antimicrobial therapy. Moreover, Salmonella Typhimurium develops resistance to various antimicrobials including, fluoroquinolones. Treating intracellular bacteria and combating drug resistance is essential to limit the infection rate. One way of overcoming these challenges is through combination therapy. In this study, Pyrogallol (PG), a polyphenol, is combined with marbofloxacin (MAR) to investigate its effect on Salmonella Typhimurium invasion and intracellular survival inhibition. The Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of PG against Salmonella Typhimurium were 128 and 256 μg/mL, respectively. The lowest fractional inhibitory concentration (FIC) index for a combination of PG and MAR was 0.5. The gentamycin protection assay revealed that PG (30 μg/mL) alone and in combination with sub-MIC of MAR inhibited 72.75 and 76.18% of the invading bacteria in Caco-2 cells, respectively. Besides, the intracellular survival of Salmonella Typhimurium was reduced by 7.69 and 74.36% in treatment with PG alone and combined with sub-MIC of MAR, respectively, which was visualized by the confocal microscopy. PG has also shown to increase the intracellular accumulation of fluoroquinolone by 15.2 and 34.9% at 30 and 100 μg/mL concentration, respectively. Quantitative real-time PCR demonstrated PG suppressed the genetic expression of hilA, invF, sipB, and acrA by 14.6, 15.4, 13.6, and 36%, respectively. However, the downregulation of hilA, invF, sipB, and acrA increased to 80, 74.6, 78, and 70.1%, in combination with sub-MIC of MAR, respectively. Similarly, PG combined with MAR inhibited the expression of sdiA, srgE, and rck genes by 78.6, 62.8, and 61.8%, respectively. In conclusion, PG has shown antimicrobial activity against Salmonella Typhimurium alone and in combination with MAR. It also inhibited invasion and intracellular survival of the bacteria through downregulation of quorum sensing, invading virulence, and efflux pump genes. Hence, PG could be a potential antimicrobial candidate which could limit the intracellular survival and replication of Salmonella Typhimurium.

ULTRASMALL BACTERIA AND PERIODONTITIS – THE NOVEL LINK

Periodontal diseases are triggered by an interaction between bacterial components of tooth associated biofilms and host immune response mechanisms. Candidate phyla radiation (CPR) bacterial group is a recently identified, but highly diverse and abundant group of ultrasmall bacteria. CPR group includes Absconditabacteria (SR1), Gracilibacteria (GN02) and Saccharibacteria (TM7). Real time PCR and metagenomics based techniques are also employed to detect CPR species. TM7 organisms has been detected in periodontitis patients, HIVpositive patients with necrotizing ulcerative periodontitis, smokers with periodontitis, aggressive periodontitis cases and in mature plaque samples procured from orthodontic treatment undergoing individuals. It is found that TM7 isolate grow as short rods or cocci in dual-species biofilms with Porphyromonas gingivalis, Prevotella intermedia, Parvimonas micra or Streptococcus gordonii. The positive association of ultrasmall bacteria or CPR microorganisms with periodontal diseases spotlights the capacity of ultrasmall bacteria to modulate the immune response. The CPR microbiome is enriched with virulence factors and is adapted to a parasitic lifestyle that leads to disrupted host homeostasis. This makes the individual susceptible to periodontal tissue destruction. In future, we should instigate researches to know more about the actions and properties of ultrasmall bacteria and their association with periodontal diseases. KEYWORDS: ultrasmall bacteria, periodontitis, Candidate Phyla Radiation (CPR) group, periodontal microbiology

Pancreatic extracellular matrix and platelet-rich plasma constructing injectable hydrogel for pancreas tissue engineering.

The development of pancreatic extracellular matrices enriched with insulin-secreting β-cells is a promising tissue engineering approach to treat type 1 diabetes. However, its long-term therapeutic efficacy is restricted by the defensive mechanism of host immune response and the lack of developed vascularization as appropriate after transplantation. Platelet-rich plasma (PRP), as an autologous platelet concentrate, contains a large number of active factors that are essential for the cell viability, vascularization, and immune regulation. In this study, we have incorporated pancreatic extracellular matrix (PEM) with PRP to develop a three-dimensional (3D) injectable PEM-PRP hydrogel to coculture and transplant rat insulinoma cells (INS-1) and human umbilical vein endothelial cells (HUVECs). Results from this study demonstrated that PEM-PRP hydrogel mimicked the biochemical compositions of native extracellular matrices, and possessed the enhanced elastic modulus and resistance to enzymatic degradation that enabled biomaterials to maintain its volume and slowly degrade. Additionally, PEM-PRP hydrogel could release growth factors in a sustained manner. In vitro, PEM-PRP hydrogel significantly promoted the viability, insulin-secreting function, and insulin gene expression of gel encapsulated INS-1 cells. Moreover, HUVECs encapsulated in PEM-PRP hydrogel were found to constitute many lumen-like structures and exhibited high expression of proangiogenic genes. In vivo transplantation of PEM-PRP hydrogel encapsulated with INS-1 cells and HUVECs improved the viability of INS-1 cells, promoted vascularization, inhibited the host inflammatory response, and reversed hyperglycemia of diabetic rats. Our study suggests that the PEM-PRP hydrogel offers excellent biocompatibility and proangiogenic property, and may serve as an effective biomaterial platform to maintain the long-term survival and function of insulin-secreting β cells.

Abstract 5135: Characterization of a data independent acquisition mass spectrometry-based workflow in the plasma of NSCLC subjects reveals host immune response mechanisms

Abstract Background: Measurement of circulating biomarkers in cancer has proven utility for early detection, differential diagnosis, and predicting pre-treatment response to therapy. More recently, circulating proteomic biomarkers for pre-treatment prediction of therapeutic response have received additional attention due to the heterogeneous responses to immunotherapies. To develop a greater understanding of the circulating plasma proteome in subjects with cancer we have optimized a depleted plasma proteomic workflow, based on label-free data independent acquisition (DIA) mass spectrometry, and applied it to plasma from subjects with late stage NSCLC. This approach provides a deep and unbiased description of the plasma proteome and the dysregulated biological pathways associated with lung cancer. Methods: Plasma samples from subjects with Stage III-IV non-small cell lung cancer (NSCLC, n = 15) and age matched healthy donors (n = 15) were depleted of 14 high abundance proteins using MARS Hu-14 spin columns (Agilent). The resulting flow through was prepared for mass spectrometry using a filter aided sample preparation method (FASP). All samples were analyzed using 2h gradients on a C18 column coupled to a Thermo Scientific Q Exactive mass spectrometer operated in DIA mode. Data was extracted using Spectronaut (Biognosys) with combined sample specific and resource spectral libraries and statistical analysis was conducted to identify disease associated biomarker candidates. Pathway analysis highlights dysregulated biological functions. Results: An overview of assay optimization will be presented which resulted in the final workflow. In summary, a comprehensive protein spectral library was created containing 1,827 unique proteins and in DIA acquisition, 1,304 proteins were quantified across all samples. Univariate statistical testing identified 162 dysregulated proteins (125 up-regulated and 37 down-regulated; q-value > 0.05 and log2 fold change > 0.58). In addition to the acute phase proteins (e.g. CRP and SAA1) which were previously verified to be elevated in subjects with NSCLC, multivariate analysis identified additional proteins that are differentially expressed between the sample groups. Most relevant to immune function was CLC (Galectin-10), which has been identified as key component supporting the suppressive function of Tregs1 and S100A9 which is a known therapeutic target associated myeloid-derived suppressor cells2. Furthermore, F13A1 was suppressed in the NSCLC samples which is known to be associated with macrophage activation. Conclusions: Multiple plasma proteins were found to be dysregulated and associated with NSCLC reflecting the host immune response via acute phase response signaling and immunosuppressive mechanisms. Several of these markers have been linked to patient outcomes and represent known therapeutic targets.1. Kubach, J., et. al. Blood 2007 110:1550-1558 2. Shen, L., et. al. Cancer Immunol Res. 2015 3(2): 136-148. Citation Format: Nicholas Dupuis, Linda Sensbach, Sebastian Muller, Lukas Reiter. Characterization of a data independent acquisition mass spectrometry-based workflow in the plasma of NSCLC subjects reveals host immune response mechanisms [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5135.

Antimicrobial and Structural Properties of Metal Ions Complexes with Thiosemicarbazide Motif and Related Heterocyclic Compounds.

Antibiotic resistance acquired by various bacterial fungal and viral pathogens poses therapeutic problems of increasing severity. Among the infections that are very difficult to treat, biofilm-associated cases are one of the most hazardous. Complex structure of a biofilm and unique physiology of the biofilm cells contribute to their extremely high resistance to environmental conditions, antimicrobial agents and the mechanisms of host immune response. Therefore, the biofilm formation, especially by multidrugresistant pathogens, is a serious medical problem, playing a pivotal role in the development of chronic and recurrent infections. These factors create a limitation for using traditional chemiotherapeutics and contribute to a request for development of new approaches for treatment of infectious diseases. Therefore, early reports on antimicrobial activity of several complexes of metal ions, bearing thiosemicarbazide or thiosemicarbazones as the ligands, gave a boost to worldwide search for new, more efficient compounds of this class, to be used as alternatives to commonly known drugs. In general, depending on the presence of other heteroatoms, these ligands may function in a di-, tri- or tetradentate forms (e.g., of N,S,-, N,N,S-, N,N,N,S-, N,N,S,S-, or N,S,O-type), which impose different coordination geometries to the resultant complexes. In the first part of this review, we describe the ways of synthesis and the structures of the ligands based on the thiosemicarbazone motif, while the second part deals with the antimicrobial activity of their complexes with selected metal ions.

Abstract B010: A survey of circulating biomarkers in subjects with NSCLC using library-based data independent acquisition mass spectrometry reveals host immune response mechanisms

Abstract Background: Identification of circulating biomarkers in cancer has proven utility in applications for early detection, differential diagnosis, predicting pre-treatment response to therapy, and treatment monitoring. More recently, circulating proteomic biomarkers have been evaluated as surrogate endpoints for early indication of benefit for immunotherapies. This last application is especially relevant during immunotherapy development where the optimal endpoint, overall survival (OS), can take longer to mature. Here, we present an unbiased survey of the circulating proteome of subjects with NSCLC to identify candidate biomarkers that may have utility in multiple stages of patient care. Methods: Unbiased, data-independent acquisition (DIA) mass spectrometry was used to analyze plasma samples from subjects with Stage III-IV non-small cell lung cancer (NSCLC, n = 15) and age matched healthy donors (n = 15), enabling simultaneous sequencing and quantification of plasma proteins. Samples were prepared for mass spectrometry and spiked with a panel of standards covering 500 plasma proteins. All samples were analyzed using 1h gradients on a C18 column coupled to a Thermo Scientific Q Exactive HF mass spectrometer. Data were extracted using Spectronaut (Biognosys) with a sample specific spectral library and statistical analysis was conducted to identify disease associated biomarker candidates. Pathway analysis highlights dysregulated biologic functions and predicts upstream regulatory pathways. Results: A protein library was created containing 771 unique proteins. In DIA acquisition, 462 proteins were quantified across all samples. Univariate statistical testing identified 26 dysregulated proteins (20 up-regulated and 6 down-regulated; q-value > 0.05 and log2 fold change > 0.58). Multivariate (PLS-DA) analysis identified c-reactive protein (CRP) and serum amyloid a (SAA1/SAA2), complement C9, S100A8/S100A9, and leucine rich glycoprotein 1 (LRG1) as the most significantly changed proteins across sample groups. Receiver operator analysis (ROC) identified S100A8 and complement C9 as the markers with the greatest diagnostic power at 93% sensitivity and 93% specificity. Significantly enriched pathways include acute phase response, complement system as well as IL-12 and IL-6 signaling. Similarly, upstream activated candidate pathways included STAT3, IL-6, and EZ2H. Conclusions: 26 proteins were identified as candidate biomarkers and reflect the host immune response via acute phase response signaling, innate immune response (complement system), and other proinflammatory stimuli. Several of these markers have been linked to patient outcomes and poor prognosis. Accurate monitoring of these proteins offers the possibility to define surrogate, molecular-based markers with multiple modes of utility. Citation Format: Nicholas Dupuis, Jakob Vowinckel, Daniel Heinzmann, Claudia Escher. A survey of circulating biomarkers in subjects with NSCLC using library-based data independent acquisition mass spectrometry reveals host immune response mechanisms [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr B010.

Mechanisms of host immune responses to human immunodeficiency virus (HIV): A mini review

In order to survive, the host has developed distinct strategies to recognize and respond effectively and rapidly to invading microorganisms present within the environment. Two types of immunity are utilized to protect the host against microbial pathogens: innate and adaptive (acquired) immunity. HIV can be transmitted via four major routes: through sexual contact, blood, perinatally (mother-to-child transmission) or via breast milk. HIV can be found as cell-free viral particles or in infected immune cells such as dendritic cells, macrophages and CD4+ T cells. Innate immune cells (e.g., dendritic cells and natural killer cells) are the first line of defence which HIV encounters upon entry to the body. The cellular immune response is induced upon the entry of HIV into the target cells (e.g., T cells) and synthesis of viral proteins. Major Histocompatibility Complex (MHC) class I on the cell surface displays the intracellularly degraded HIV peptide fragments for recognition by T-cell receptors (TCR) on CD8+ T cells. The paper was aimed to review host immune response to Human Immunodeficiency Virus (HIV).

Analysis of expression profiles of long noncoding RNAs and mRNAs in brains of mice infected by rabies virus by RNA sequencing

Rabies, caused by rabies virus (RABV), is still the deadliest infectious disease. Mechanism of host immune response upon RABV infection is not yet fully understood. Accumulating evidences suggest that long noncoding RNAs (lncRNAs) plays key roles in host antiviral responses. However, expression profile and function of lncRNAs in RABV infection remain unclear. In the present study, expression profile of lncRNAs and mRNAs profiles were investigated in RABV-infected brain tissues of mice by RNA sequencing. A total of 140 lncRNAs and 3,807 mRNAs were differentially expressed in RABV-infected animals. The functional annotation and enrichment analysis using Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed that differentially expressed transcripts were predominantly involved in signaling pathways related to host immune response. The expression profiles of the selected lncRNAs in brains of mice during RABV infections were verified by quantitative real time polymerase chain reaction (qRT-PCR). To our knowledge, this is the first report to profile the lncRNA expression in RABV infected mice. Our findings provide insights into understanding the role of lncRNAs in host immune response against RABV infection.

Autoimmune hemolytic anemia associated with babesiosis

BackgroundBabesiosis is endemic in selected areas in North America. Babesia infection is commonly associated with anemia, thrombocytopenia, hyponatremia and elevated liver enzymes. Autoimmune hemolytic anemia (AIHA) is known to be caused by parasitic and viral infections but has not been well characterized.Case presentationWe describe two cases diagnosed with babesiosis triggering severe AIHA. One case had history of splenectomy, and the other was an elderly patient. Older, immunocompromised and asplenic patients may be particularly at risk for post-babesiosis AIHA (PB-AIHA).ConclusionsThe pathogenesis for conventional AIHA and PB-AIHA appears to be different, since splenectomy is a treatment for conventional AIHA, whereas PB-AIHA is seen more often in asplenic patients. Further investigation into this intriguing mechanism of host immune response to babesiosis may help to elucidate the overall mechanism of infection- triggered AIHA.