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PLoS Neglected Tropical Diseases 2015Leishmaniasis is a complex disease in which clinical outcome depends on factors such as parasite species, host genetics and immunity and vector species. In Brazil,... (Comparative Study)
Comparative Study
BACKGROUND
Leishmaniasis is a complex disease in which clinical outcome depends on factors such as parasite species, host genetics and immunity and vector species. In Brazil, Leishmania (Viannia) braziliensis is a major etiological agent of cutaneous (CL) and mucosal leishmaniasis (MCL), a disfiguring form of the disease, which occurs in ~10% of L. braziliensis-infected patients. Thus, clinical isolates from patients with CL and MCL may be a relevant source of information to uncover parasite factors contributing to pathogenesis. In this study, we investigated two pairs of L. (V.) braziliensis isolates from mucosal (LbrM) and cutaneous (LbrC) sites of the same patient to identify factors distinguishing parasites that migrate from those that remain at the primary site of infection.
METHODOLOGY/PRINCIPAL FINDINGS
We observed no major genomic divergences among the clinical isolates by molecular karyotype and genomic sequencing. RT-PCR revealed that the isolates lacked Leishmania RNA virus (LRV). However, the isolates exhibited distinct in vivo pathogenesis in BALB/c mice; the LbrC isolates were more virulent than the LbrM isolates. Metabolomic analysis revealed significantly increased levels of 14 metabolites in LbrC parasites and 31 metabolites in LbrM parasites that were mainly related to inflammation and chemotaxis. A proteome comparative analysis revealed the overexpression of LbrPGF2S (prostaglandin f2-alpha synthase) and HSP70 in both LbrC isolates. Overexpression of LbrPGF2S in LbrC and LbrM promastigotes led to an increase in infected macrophages and the number of amastigotes per cell at 24-48 h post-infection (p.i.).
CONCLUSIONS/SIGNIFICANCE
Despite sharing high similarity at the genome structure and ploidy levels, the parasites exhibited divergent expressed genomes. The proteome and metabolome results indicated differential profiles between the cutaneous and mucosal isolates, primarily related to inflammation and chemotaxis. BALB/c infection revealed that the cutaneous isolates were more virulent than the mucosal parasites. Furthermore, our data suggest that the LbrPGF2S protein is a candidate to contribute to parasite virulence profiles in the mammalian host.
Topics: Animals; Brazil; Disease Models, Animal; Gene Expression Profiling; Humans; Leishmania braziliensis; Leishmaniasis, Mucocutaneous; Metabolome; Mice, Inbred BALB C; Mucous Membrane; Proteome; Skin
PubMed: 26366580
DOI: 10.1371/journal.pntd.0004018 -
International Reviews of Immunology 2009To date, most HIV vaccine strategies have focused on parenteral immunization and systemic immunity. These approaches have not yielded the efficacious HIV vaccine... (Review)
Review
To date, most HIV vaccine strategies have focused on parenteral immunization and systemic immunity. These approaches have not yielded the efficacious HIV vaccine urgently needed to control the AIDS pandemic. As HIV is primarily mucosally transmitted, efforts are being re-focused on mucosal vaccine strategies, in spite of complexities of immune response induction and evaluation. Here, we outline issues in mucosal vaccine design and illustrate strategies with examples from the recent literature. Development of a successful HIV vaccine will require in-depth understanding of the mucosal immune system, knowledge that ultimately will benefit vaccine design for all mucosally transmitted infectious agents.
Topics: AIDS Vaccines; Animals; Drug Administration Routes; HIV Infections; Humans; Immunity, Mucosal; Mucous Membrane; Receptors, Cell Surface; SAIDS Vaccines; Simian Acquired Immunodeficiency Syndrome; Vaccination
PubMed: 19241252
DOI: 10.1080/08830180802684331 -
FEMS Immunology and Medical Microbiology Dec 2006This review examines the question of whether exercise can be used as an experimental model to further our understanding of innate antimicrobial peptides and proteins... (Review)
Review
This review examines the question of whether exercise can be used as an experimental model to further our understanding of innate antimicrobial peptides and proteins (AMPs) and their role in susceptibility to infection at mucosal surfaces. There is strong evidence to suggest that AMPs, in combination with cellular and physical factors, play an important role in preventing infection. Although AMPs act directly on microorganisms, there is increasing recognition that they also exert their protective effect via immunomodulatory mechanisms, especially in noninflammatory conditions. Further studies that manipulate physiologically relevant concentrations of AMPs are required to shed light on the role they play in reducing susceptibility to infection. Evidence shows that in various form prolonged and/or exhaustive exercise is a potent modulator of the immune system, which can either sharpen or blunt the immune response to pathogens. The intensity and duration of exercise can be readily controlled in experimental settings to manipulate the degree of physical stress. This would allow for an investigation into a potential dose-response effect between exercise and AMPs. In addition, the use of controlled exercise could provide an experimental model by which to examine whether changes in the concentration of AMPs alters susceptibility to illness.
Topics: Animals; Exercise; Humans; Immunity, Innate; Infections; Mucous Membrane; Physical Conditioning, Animal; Physical Exertion; Stress, Physiological; Stress, Psychological
PubMed: 17132140
DOI: 10.1111/j.1574-695X.2006.00132.x -
The New England Journal of Medicine Sep 2018
Topics: Adult; Humans; Male; Mucositis; Mycoplasma Infections; Mycoplasma pneumoniae; Polymerase Chain Reaction
PubMed: 30257151
DOI: 10.1056/NEJMicm1614484 -
Journal of Immunology (Baltimore, Md. :... Dec 2007Whether mucosal immunization is required for optimal protective CD8 T cell memory at mucosal surfaces is controversial. In this study, using an adoptive transfer system,...
Whether mucosal immunization is required for optimal protective CD8 T cell memory at mucosal surfaces is controversial. In this study, using an adoptive transfer system, we compare the efficacy of two routes of acute lymphocytic choriomeningitis viral infection on the generation, maintenance, and localization of Ag-specific CD8 T cells in tissues, including the vaginal mucosa. Surprisingly, at day 8, i.p. infection results in higher numbers of Ag-specific CD8 T cells in the vaginal mucosa and iliac lymph node, as well as 2-3x more Ag-specific CD8 T cells that coexpress both IFN-gamma and TNF-alpha in comparison to the intranasal route of infection. Expression of the integrin/activation marker CD103 (alphaEbeta7) is low on vaginal mucosal Ag-specific CD8 T cells in comparison to gut mucosal intraepithelial lymphocytes. At memory, no differences are evident in the number, cytokine production, or protective function of Ag-specific CD8 T cells in the vaginal mucosa comparing the two routes of infection. However, differences persist in the cytokine profile of genital tract vs peripheral Ag-specific CD8 T cells. So although the initial route of infection, as well as tissue microenvironment, appear to influence both the magnitude and quality of the effector CD8 T cell response, both systemic and mucosal infection are equally effective in the differentiation of protective memory CD8 T cell responses against vaginal pathogenic challenge.
Topics: Animals; Antigens, CD; Arenaviridae Infections; CD8-Positive T-Lymphocytes; Cytokines; Female; Immunity, Mucosal; Immunologic Memory; Integrin alpha Chains; Integrins; Lymphocytic choriomeningitis virus; Mice; Mucous Membrane; Vagina
PubMed: 18056354
DOI: 10.4049/jimmunol.179.12.8122 -
Current Topics in Microbiology and... 2012Bioterrorism is the deliberate release of biological toxins, pathogenic viruses, bacteria, parasites, or other infectious agents into the public sphere with the... (Review)
Review
Bioterrorism is the deliberate release of biological toxins, pathogenic viruses, bacteria, parasites, or other infectious agents into the public sphere with the objective of causing panic, illness, and/or death on a local, regional, or possibly national scale. The list of potential biological agents compiled by the Centers for Disease Control and Prevention is long and diverse. However, a trait common to virtually all the potential bioterrorism agents is the fact that they are likely to be disseminated by either aerosol or in food/water supplies with the intention of targeting the mucosal surfaces of the respiratory or gastrointestinal tracts, respectively. In some instances, inhalation or ingestion would mimic the natural route by which humans are exposed to these agents. In other instances, (e.g., the inhalation of a toxin is normally associated with food borne illness), it would represent an unnatural route of exposure. For most potential bioterrorism agents, the respiratory or gastrointestinal mucosa may simply serve as a route of entry by which they gain access to the systemic compartment where intoxication/replication occurs. For others, however, the respiratory or gastrointestinal mucosa is the primary tissue associated with pathogenesis, and therefore, the tissue for which countermeasures must be developed.
Topics: Animals; Bioterrorism; Humans; Infection Control; Infections; Mucous Membrane; United States; Vaccines
PubMed: 21461982
DOI: 10.1007/82_2011_122 -
Antiviral Research Dec 2010A combination of prevention and treatment modalities will be needed to successfully control the global spread of HIV. Microbicides, drug products topically applied to... (Review)
Review
A combination of prevention and treatment modalities will be needed to successfully control the global spread of HIV. Microbicides, drug products topically applied to mucosal surfaces to prevent HIV infection, are one of these biomedical interventions that hold great promise. In order to be efficacious, microbicides must overcome several challenges imposed by the mucosal microenvironment they intend to protect and the mischievous human immunodeficiency virus with its enormous capacity to adapt. Recent data, however, supports the establishment of the primo-infection by only a small number of founder viruses, which are highly vulnerable to microbicidal intervention at the initial stages of mucosal invasion. The biological foundation of these challenges and opportunities in microbicide development is explored in this review. This article forms part of a special supplement on presentations covering HIV transmission and microbicides, based on the symposium "Trends in Microbicide Formulations", held on 25 and 26 January 2010, Arlington, VA.
Topics: Administration, Intravaginal; Anti-HIV Agents; Anti-Infective Agents, Local; CD4-Positive T-Lymphocytes; Clinical Trials as Topic; Dendritic Cells; Drug Design; Epithelial Cells; Female; HIV; HIV Infections; Humans; Male; Mucous Membrane; Vagina; Virus Attachment
PubMed: 21109065
DOI: 10.1016/j.antiviral.2010.09.011 -
Scientific Reports Jun 2020Self-touch may promote the transfer of microorganisms between body parts or surfaces to mucosa. In overt videography of a post-graduate office, students spent 9% of...
Self-touch may promote the transfer of microorganisms between body parts or surfaces to mucosa. In overt videography of a post-graduate office, students spent 9% of their time touching their own hair, face, neck, and shoulders (HFNS). These data were collected from 274,000 s of surveillance video in a Chinese graduate student office. The non-dominant hand contributed to 66.1% of HFNS-touches. Most importantly, mucous membranes were touched, on average, 34.3 (SE = 2.4) times per hour, which the non-dominant hand contributed to 240% more than the dominant hand. Gender had no significant effect on touch frequency, but a significant effect on duration per touch. The duration per touch on the HFNS was fitted with a log-log linear distribution. Touch behaviour analysis included surface combinations and a probability matrix for sequential touches of 20 sub-surfaces. These findings may partly explain the observed variation in the literature regarding the microbiome community distribution on human skin, supporting the importance of indirect contact transmission route in some respiratory disease transmission and providing data for risk analysis of infection spread and control.
Topics: Adult; Face; Female; Functional Laterality; Hand; Humans; Infections; Male; Movement; Mucous Membrane; Skin; Touch; Video Recording; Young Adult
PubMed: 32591572
DOI: 10.1038/s41598-020-67521-5 -
Future Microbiology Jan 2010Herpes simplex virus (HSV) serotypes 1 and 2 establish lifelong infections that can produce reactivated pools of virus at mucosal sites where primary infections were... (Review)
Review
Herpes simplex virus (HSV) serotypes 1 and 2 establish lifelong infections that can produce reactivated pools of virus at mucosal sites where primary infections were initiated. No approved vaccines are available. To break the transmission cycle, interventions must either prevent infection or reduce infectivity at mucosal sites. This article discusses the recent experimental successes of immunoprophylactic and therapeutic compounds that enhance resistance and/or reduce viral loads at genital and ocular mucosa. Current data indicate Toll-like receptor agonists and selected immunomodulating compounds effectively increase the HSV infection threshold and hold promise for genital prophylaxis. Similarly, immunization at genital and extragenital mucosal sites is discussed. Finally, preclinical success with novel immunotherapies for ocular HSV that address herpetic keratitis and corneal blindness is reviewed.
Topics: Chemoprevention; Herpes Simplex; Herpesvirus Vaccines; Humans; Immunologic Factors; Mucous Membrane
PubMed: 20020827
DOI: 10.2217/fmb.09.111 -
Immunological Reviews Jul 2014Immune responses to gastrointestinal nematodes have been studied extensively for over 80 years and intensively investigated over the last 30-40 years. The use of... (Review)
Review
Immune responses to gastrointestinal nematodes have been studied extensively for over 80 years and intensively investigated over the last 30-40 years. The use of laboratory models has led to the discovery of new mechanisms of protective immunity and made major contributions to our fundamental understanding of both innate and adaptive responses. In addition to host protection, it is clear that immunoregulatory processes are common in infected individuals and resistance often operates alongside modulation of immunity. This review aims to discuss the recent discoveries in both host protection and immunoregulation against gastrointestinal nematodes, placing the data in context of the specific life cycles imposed by the different parasites studied and the future challenges of considering the mucosal/immune axis to encompass host, parasite, and microbiome in its widest sense.
Topics: Adaptive Immunity; Animals; Chronic Disease; Gastrointestinal Tract; Host-Parasite Interactions; Humans; Immunity, Innate; Immunomodulation; Mucous Membrane; Nematoda; Nematode Infections; T-Lymphocyte Subsets
PubMed: 24942690
DOI: 10.1111/imr.12188