scholarly journals Liver- and Spleen-Specific Immune Responses in Experimental Leishmania martiniquensis Infection in BALB/c Mice

2021 ◽  
Vol 8 ◽  
Author(s):  
Woraporn Sukhumavasi ◽  
Theerayuth Kaewamatawong ◽  
Nawaphat Somboonpoonpol ◽  
Montakan Jiratanh ◽  
Juntra Wattanamethanont ◽  
...  
Keyword(s):  
Immune Responses ◽  
Persistent Infection ◽  
Clinical Manifestations ◽  
Chronic Phase ◽  
Parasite Burden ◽  
The United States ◽  
Murine Models ◽  
Hepatic Granuloma ◽  
Organ Specific ◽  
Th1 Cytokines

Leishmania martiniquensis is a neglected cause of an emerging leishmaniasis in many countries, including France, Germany, Switzerland, the United States of America, Myanmar, and Thailand, with different clinical manifestations ranging from asymptomatic, cutaneous (CL), visceral (VL), and atypically disseminated CL and VL. The persistence of parasites and the recurrence of the disease after treatment are challenges in controlling the disease. To explore efficient prophylaxis and therapy, this study aimed to investigate infection outcome and organ-specific immune responses after inoculation with L. martiniquensis (MHOM/TH/2011/PG; 5 x 106 promastigotes) in BALB/c mice via intravenous and intraperitoneal routes. A quantitative PCR technique, targeting L. martiniquensis ITS1, was primarily established to estimate the parasite burden. We found that the infection in the liver resolved; however, persistent infection was observed in the spleen. Histopathology with Leishmania-specific immunostaining revealed efficient hepatic granuloma formation, while splenic disorganization with parasitized macrophages at different locations was demonstrated. The mRNA expression of Th1 cytokines (IFN-γ, TNF-α, IL-12p40) and iNOS in the liver and spleen was upregulated. In addition, high expression of IL-10 was observed in the spleen in the chronic phase, revealing a significant moderate correlation with the parasite persistence [r(12) = 0.72, P = 0.009]. Further clarification of the mechanisms of persistent infection and experimental infection in immunosuppressed murine models are warranted.

scholarly journals Current Understanding of West Nile Virus Clinical Manifestations, Immune Responses, Neuroinvasion, and Immunotherapeutic Implications

Pathogens ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 193 ◽  
Author(s):  
Fengwei Bai ◽  
E. Ashley Thompson ◽  
Parminder J. S. Vig ◽  
A. Arturo Leis
Keyword(s):  
New York ◽  
West Nile Virus ◽  
Immune Responses ◽  
Clinical Manifestations ◽  
The United States ◽  
Current Understanding ◽  
Therapeutic Interventions ◽  
Clinical Practices ◽  
West Nile ◽  
Neuroinvasive Disease

West Nile virus (WNV) is the most common mosquito-borne virus in North America. WNV-associated neuroinvasive disease affects all ages, although elderly and immunocompromised individuals are particularly at risk. WNV neuroinvasive disease has killed over 2300 Americans since WNV entered into the United States in the New York City outbreak of 1999. Despite 20 years of intensive laboratory and clinical research, there are still no approved vaccines or antivirals available for human use. However, rapid progress has been made in both understanding the pathogenesis of WNV and treatment in clinical practices. This review summarizes our current understanding of WNV infection in terms of human clinical manifestations, host immune responses, neuroinvasion, and therapeutic interventions.

scholarly journals Influenza vaccination and the risk of COVID-19 infection and severe illness in older adults in the United States

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kelly Huang ◽  
Shu-Wen Lin ◽  
Wang-Huei Sheng ◽  
Chi-Chuan Wang
Keyword(s):  
Immune Responses ◽  
Influenza Vaccine ◽  
Influenza Vaccination ◽  
The United States ◽  
Cross Sectional Study ◽  
Severe Illness ◽  
Cross Sectional ◽  
Global Pandemic ◽  
Study Population ◽  
Health Database

AbstractThe coronavirus disease of 2019 (COVID-19) has caused a global pandemic and led to nearly three million deaths globally. As of April 2021, there are still many countries that do not have COVID-19 vaccines. Before the COVID-19 vaccines were developed, some evidence suggested that an influenza vaccine may stimulate nonspecific immune responses that reduce the risk of COVID-19 infection or the severity of COVID-19 illness after infection. This study evaluated the association between influenza vaccination and the risk of COVID-19 infection. We conducted a retrospective cross-sectional study with data from July 1, 2019, to June 30, 2020 with the Claims data from Symphony Health database. The study population was adults age 65 years old or older who received influenza vaccination between September 1 and December 31 of 2019. The main outcomes and measures were odds of COVID-19 infection and severe COVID-19 illness after January 15, 2020. We found the adjusted odds ratio (aOR) of COVID-19 infection risk between the influenza-vaccination group and no-influenza-vaccination group was 0.76 (95% confidence interval (CI), 0.75–0.77). Among COVID-19 patients, the aOR of developing severe COVID-19 illness was 0.72 (95% CI, 0.68–0.76) between the influenza-vaccination group and the no-influenza-vaccination group. When the influenza-vaccination group and the other-vaccination group were compared, the aOR of COVID-19 infection was 0.95 (95% CI, 0.93–0.97), and the aOR of developing a severe COVID-19 illness was 0.95 (95% CI, 0.80–1.13). The influenza vaccine may marginally protect people from COVID-19 infection.

scholarly journals Upregulated Expression of Cytotoxicity-Related Genes in IFN-γKnockout Mice withSchistosoma japonicumInfection

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Xiaotang Du ◽  
Jingjiao Wu ◽  
Meijuan Zhang ◽  
Yanan Gao ◽  
Donghui Zhang ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Schistosoma Japonicum ◽  
Fas Ligand ◽  
Acute Infection ◽  
Acquired Resistance ◽  
Parasite Burden ◽  
Cytotoxic T Cell ◽  
Igg Antibody

It is well accepted that IFN-γis important to the development of acquired resistance against murine schistosomiasis. However, thein vivorole of this immunoregulatory cytokine in helminth infection needs to be further investigated. In this study, parasite burden and host immune response were observed in IFN-γknockout mice (IFNg KO) infected withSchistosoma japonicumfor 6 weeks. The results suggested that deficiency in IFN-γled to decreased egg burden in mice, with low schistosome-specific IgG antibody response and enhanced activation of T cells during acute infection. Microarray and qRT-PCR data analyses showed significant upregulation of some cytotoxicity-related genes, including those from the granzyme family, tumor necrosis factor, Fas Ligand, and chemokines, in the spleen cells of IFNg KO mice. Furthermore, CD8+cells instead of NK cells of IFNg KO mice exhibited increased transcription of cytotoxic genes compared with WT mice. Additionally,Schistosoma japonicum-specific egg antigen immunization also could activate CD8+T cells to upregulate the expression of cytotoxic genes in IFNg KO mice. Our data suggest that IFN-γis not always a positive regulator of immune responses. In certain situations, the disruption of IFN-γsignaling may up-regulate the cytotoxic T-cell-mediated immune responses to the parasite.

Postherpetic Neuralgia: A Patient’s and a Physician’s Perspective

2016 ◽  
Author(s):  
James H. Diaz
Keyword(s):  
Neuropathic Pain ◽  
Herpes Zoster ◽  
Postherpetic Neuralgia ◽  
Clinical Manifestations ◽  
The United States ◽  
Evidence Based ◽  
Pain Medicine ◽  
High Prevalence ◽  
Antiviral Medications ◽  
Physician’S Perspective

Herpes zoster can plague anyone who has had varicella or has received the varicella or chickenpox vaccine. The incidence of herpes zoster increases with age and rises exponentially after 60 years of age. Postherpetic neuralgia (PHN) may occur after herpes zoster at any age but typically occurs after 50 years of age, with over 40% of persons over 60 years of age suffering from PHN after a shingles attack. Up to 1 million new cases of herpes zoster and 200,000 new cases of PHN may now be anticipated in the United States every year, with the incidence rate increasing as the population grows and ages with prolonged life expectancies. Although new antiviral medications will improve and shorten the course of herpes zoster, they do not guarantee the prevention of PHN. Given the high prevalence of PHN in an aging population and the availability of primary prevention by vaccination, the objectives of this review are to describe the epidemiology, pathophysiology, and clinical manifestations of zoster and PHN and to recommend a combination of strategies for the clinical management and prevention of PHN. This review contains 6 figures, 4 tables and 13 references Key words: evidence-based pain medicine, herpes zoster, neuropathic pain, postherpetic neuralgia

Abstract 116: Detrimental Role of Toll-Like Receptor 4 in Cardiovirus-Induced Myocarditis

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Fumitaka Sato ◽  
Seiichi Omura ◽  
Nicholas E Martinez ◽  
Eiichiro Kawai ◽  
Ganta V Chaitanya ◽  
...  
Keyword(s):  
Immune Responses ◽  
Acute Phase ◽  
Viral Entry ◽  
Viral Myocarditis ◽  
Chronic Phase ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tlr4 Ligand ◽  
Ifn Γ ◽  
Deficient Mice

Picornavirus infections have been known as a leading cause of viral myocarditis in humans. Theiler’s murine encephalomyelitis virus (TMEV) belongs to the genus Cardiovirus, the family Picornaviridae and was reported to cause inflammation in the heart in one manuscript, while its pathomechanism is unclear. In viral myocarditis, viral replication in the heart and/or immune responses against virus as well as heart-antigen (autoimmunity) can contribute to the pathogenesis. Toll-like receptors (TLRs) are pattern recognition receptors (PRRs) that are important for recognizing pathogens as well as triggering innate immunity. Among TLRs, TLR4 has been demonstrated to play important roles in virus-mediated pathology: 1) TLR4 can contribute to viral entry in some viruses, 2) TLR4 may mediate tissue damage by anti-virus immune responses (immunopathology), 3) high levels of TLR4 expression were observed in the heart of patients with dilated cardiomyopathy following acute viral myocarditis, and 4) some viruses can bind to lipopolysaccharide (LPS), which is a TLR4 ligand. To determine the role of TLR4 in TMEV-induced myocarditis, we infected male C3H/HeJ (TLR4-deficient) and C3H/HeNtac (control TLR4+) mice with the DA strain of TMEV. We harvested the hearts and spleens on days 6 and 7 (acute phase) or days 63 and 64 (chronic phase) post-infection. Cardiac pathology was evaluated by hematoxylin and eosin staining and production of pro-inflammatory cytokines, interleukin (IL)-17A and interferon (IFN)-γ, from spleen cells was measured by an enzyme-linked immunosorbent assay (ELISA). In both mice, mild myocarditis was observed during the acute phase of TMEV infection. During the chronic phase, both mice developed severe pathology in the heart, including basophilic degeneration and calcification. However, the incidence of myocarditis was higher in control mice than TLR4-deficient mice. IL-17A and IFN-γ production was higher in control mice than in TLR4-deficient mice (control vs. TLR4-deficient mice, acute phase: IL-17A, 196 vs. 146 pg/ml; IFN-γ, 72 vs. 39 ng/ml; chronic phase: IL-17A, 290 vs. 229 pg/ml; IFN- γ, 142 vs. 88 ng/ml). These results suggest that TLR4 may be detrimental in TMEV-induced myocarditis by increasing pro-inflammatory cytokine production.

scholarly journals Spatial metabolomics identifies localized chemical changes in heart tissue during chronic cardiac Chagas Disease

2021 ◽  
Vol 15 (10) ◽  
pp. e0009819
Author(s):  
Danya A. Dean ◽  
Gautham Gautham ◽  
Jair L. Siqueira-Neto ◽  
James H. McKerrow ◽  
Pieter C. Dorrestein ◽  
...  
Keyword(s):  
Chagas Disease ◽  
Neglected Tropical Diseases ◽  
Clinical Manifestations ◽  
Parasite Burden ◽  
Heart Tissue ◽  
Cardiac Symptoms ◽  
Heart Region ◽  
Contaminated Food ◽  
Vector Borne ◽  
Insight Into

Chagas disease (CD), caused by the parasite Trypanosoma cruzi, is one of nineteen neglected tropical diseases. CD is a vector-borne disease transmitted by triatomines, but CD can also be transmitted through blood transfusions, organ transplants, T. cruzi-contaminated food and drinks, and congenital transmission. While endemic to the Americas, T. cruzi infects 7–8 million people worldwide and can induce severe cardiac symptoms including apical aneurysms, thromboembolisms and arrhythmias during the chronic stage of CD. However, these cardiac clinical manifestations and CD pathogenesis are not fully understood. Using spatial metabolomics (chemical cartography), we sought to understand the localized impact of chronic CD on the cardiac metabolome of mice infected with two divergent T. cruzi strains. Our data showed chemical differences in localized cardiac regions upon chronic T. cruzi infection, indicating that parasite infection changes the host metabolome at specific sites in chronic CD. These sites were distinct from the sites of highest parasite burden. In addition, we identified acylcarnitines and glycerophosphocholines as discriminatory chemical families within each heart region, comparing infected and uninfected samples. Overall, our study indicated global and positional metabolic differences common to infection with different T. cruzi strains and identified select infection-modulated pathways. These results provide further insight into CD pathogenesis and demonstrate the advantage of a systematic spatial perspective to understand infectious disease tropism.

scholarly journals Combining Photodynamic Therapy with Immunostimulatory Nanoparticles Elicits Effective Anti-Tumor Immune Responses in Preclinical Murine Models

Pharmaceutics ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 1470
Author(s):  
Ruben Victor Huis in ‘t Veld ◽  
Candido G. Da Silva ◽  
Martine J. Jager ◽  
Luis J. Cruz ◽  
Ferry Ossendorp
Keyword(s):  
T Cells ◽  
Photodynamic Therapy ◽  
Immune Responses ◽  
Solid Tumors ◽  
Cd8 T Cells ◽  
Vaccination Strategy ◽  
Neutrophil Infiltration ◽  
Poly I:C ◽  
Murine Models ◽  
Human Papillomavirus 16

Photodynamic therapy (PDT) has shown encouraging but limited clinical efficacy when used as a standalone treatment against solid tumors. Conversely, a limitation for immunotherapeutic efficacy is related to the immunosuppressive state observed in large, advanced tumors. In the present study, we employ a strategy, in which we use a combination of PDT and immunostimulatory nanoparticles (NPs), consisting of poly(lactic-co-glycolic) acid (PLGA)-polyethylene glycol (PEG) particles, loaded with the Toll-like receptor 3 (TLR3) agonist poly(I:C), the TLR7/8 agonist R848, the lymphocyte-attracting chemokine, and macrophage inflammatory protein 3α (MIP3α). The combination provoked strong anti-tumor responses, including an abscopal effects, in three clinically relevant murine models of cancer: MC38 (colorectal), CT26 (colorectal), and TC-1 (human papillomavirus 16-induced). We show that the local and distal anti-tumor effects depended on the presence of CD8+ T cells. The combination elicited tumor-specific oncoviral- or neoepitope-directed CD8+ T cells immune responses against the respective tumors, providing evidence that PDT can be used as an in situ vaccination strategy against cancer (neo)epitopes. Finally, we show that the treatment alters the tumor microenvironment in tumor-bearing mice, from cold (immunosuppressed) to hot (pro-inflammatory), based on greater neutrophil infiltration and higher levels of inflammatory myeloid and CD8+ T cells, compared to untreated mice. Together, our results provide a rationale for combining PDT with immunostimulatory NPs for the treatment of solid tumors.

scholarly journals Technologies for Detection of Babesia microti: Advances and Challenges

Pathogens ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1563
Author(s):  
Scott Meredith ◽  
Miranda Oakley ◽  
Sanjai Kumar
Keyword(s):  
United States ◽  
Early Stage ◽  
Parasite Burden ◽  
The United States ◽  
Babesia Microti ◽  
Current Status ◽  
Low Grade ◽  
Babesia Species ◽  
Technological Advances ◽  
Human Babesiosis

The biology of intraerythrocytic Babesia parasites presents unique challenges for the diagnosis of human babesiosis. Antibody-based assays are highly sensitive but fail to detect early stage Babesia infections prior to seroconversion (window period) and cannot distinguish between an active infection and a previously resolved infection. On the other hand, nucleic acid-based tests (NAT) may lack the sensitivity to detect window cases when parasite burden is below detection limits and asymptomatic low-grade infections. Recent technological advances have improved the sensitivity, specificity and high throughput of NAT and the antibody-based detection of Babesia. Some of these advances include genomics approaches for the identification of novel high-copy-number targets for NAT and immunodominant antigens for superior antigen and antibody-based assays for Babesia. Future advances would also rely on next generation sequencing and CRISPR technology to improve Babesia detection. This review article will discuss the historical perspective and current status of technologies for the detection of Babesia microti, the most common Babesia species causing human babesiosis in the United States, and their implications for early diagnosis of acute babesiosis, blood safety and surveillance studies to monitor areas of expansion and emergence and spread of Babesia species and their genetic variants in the United States and globally.

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