-
Frontiers in Cellular and Infection... 2018is a Gram-negative pathogen that has a large accessory genome of plasmids and chromosomal gene loci. This accessory genome divides strains into opportunistic,... (Review)
Review
is a Gram-negative pathogen that has a large accessory genome of plasmids and chromosomal gene loci. This accessory genome divides strains into opportunistic, hypervirulent, and multidrug-resistant groups and separates from two closely related species, and . Some strains of act as opportunistic pathogens, infecting critically ill and immunocompromised patients. These are a common cause of health-care associated infections including pneumonia, urinary tract infections (UTIs), and bloodstream infections. and are often clinically indistinguishable from opportunistic . Other strains of are hypervirulent, infecting healthy people in community settings and causing severe infections including pyogenic liver abscess, endophthalmitis, and meningitis. A third group of encode carbapenemases, making them highly antibiotic-resistant. These strains act as opportunists but are exceedingly difficult to treat. All of these groups of and related species can colonize the gastrointestinal tract, and the accessory genome may determine if a colonizing strain remains asymptomatic or progresses to cause disease. This review will explore the associations between colonization and infection with opportunistic, antibiotic-resistant, and hypervirulent strains and the role of the accessory genome in distinguishing these groups and related species. As infections become progressively more difficult to treat in the face of antibiotic resistance and hypervirulent strains, an increased understanding of the epidemiology and pathogenesis of these bacteria is vital.
Topics: Anti-Bacterial Agents; Community-Acquired Infections; Cross Infection; Drug Resistance, Bacterial; Genes, Bacterial; Genome, Bacterial; Humans; Klebsiella Infections; Klebsiella pneumoniae; Mucous Membrane; Opportunistic Infections; Virulence
PubMed: 29404282
DOI: 10.3389/fcimb.2018.00004 -
Frontiers in Immunology 2018Vaccination is the process of administering immunogenic formulations in order to induce or harness antigen (Ag)-specific antibody and T cell responses in order to... (Review)
Review
Vaccination is the process of administering immunogenic formulations in order to induce or harness antigen (Ag)-specific antibody and T cell responses in order to protect against infections. Important successes have been obtained in protecting individuals against many deleterious pathological situations after parenteral vaccination. However, one of the major limitations of the current vaccination strategies is the administration route that may not be optimal for the induction of immunity at the site of pathogen entry, i.e., mucosal surfaces. It is now well documented that immune responses along the genital, respiratory, or gastrointestinal tracts have to be elicited locally to ensure efficient trafficking of effector and memory B and T cells to mucosal tissues. Moreover, needle-free mucosal delivery of vaccines is advantageous in terms of safety, compliance, and ease of administration. However, the quest for mucosal vaccines is challenging due to (1) the fact that Ag sampling has to be performed across the epithelium through a relatively limited number of portals of entry; (2) the deleterious acidic and proteolytic environment of the mucosae that affect the stability, integrity, and retention time of the applied Ags; and (3) the tolerogenic environment of mucosae, which requires the addition of adjuvants to elicit efficient effector immune responses. Until now, only few mucosally applicable vaccine formulations have been developed and successfully tested. In animal models and clinical trials, the use of lipidic structures such as liposomes, virosomes, immune stimulating complexes, gas-filled microbubbles and emulsions has proven efficient for the mucosal delivery of associated Ags and the induction of local and systemic immune reponses. Such particles are suitable for mucosal delivery because they protect the associated payload from degradation and deliver concentrated amounts of Ags specialized sampling cells (microfold cells) within the mucosal epithelium to underlying antigen-presenting cells. The review aims at summarizing recent development in the field of mucosal vaccination using lipid-based particles. The modularity ensured by tailoring the lipidic design and content of particles, and their known safety as already established in humans, make the continuing appraisal of these vaccine candidates a promising development in the field of targeted mucosal vaccination.
Topics: Animals; Drug Delivery Systems; Humans; Immunity, Mucosal; Infections; Lipids; Microbubbles; Mucous Membrane; Vaccination; Vaccines
PubMed: 29563912
DOI: 10.3389/fimmu.2018.00431 -
Immunological Reviews Jul 2013Recent advances in the immunology, pathogenesis, and prevention of human immunodeficiency virus (HIV) infection continue to reveal clues to the mechanisms involved in... (Review)
Review
Recent advances in the immunology, pathogenesis, and prevention of human immunodeficiency virus (HIV) infection continue to reveal clues to the mechanisms involved in the progressive immunodeficiency attributed to infection, but more importantly have shed light on the correlates of immunity to infection and disease progression. HIV selectively infects, eliminates, and/or dysregulates several key cells of the human immune system, thwarting multiple arms of the host immune response, and inflicting severe damage to mucosal barriers, resulting in tissue infiltration of 'symbiotic' intestinal bacteria and viruses that essentially become opportunistic infections promoting systemic immune activation. This leads to activation and recruitment or more target cells for perpetuating HIV infection, resulting in persistent, high-level viral replication in lymphoid tissues, rapid evolution of resistant strains, and continued evasion of immune responses. However, vaccine studies and studies of spontaneous controllers are finally providing correlates of immunity from protection and disease progression, including virus-specific CD4(+) T-cell responses, binding anti-bodies, innate immune responses, and generation of antibodies with potent antibody-dependent cell-mediated cytotoxicity activity. Emerging correlates of immunity indicate that prevention of HIV infection may be possible through effective vaccine strategies that protect and stimulate key regulatory cells and immune responses in susceptible hosts. Furthermore, immune therapies specifically directed toward boosting specific aspects of the immune system may eventually lead to a cure for HIV-infected patients.
Topics: AIDS Vaccines; Animals; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Female; Gastrointestinal Tract; HIV Infections; HIV-1; Humans; Immunity, Humoral; Immunity, Innate; Immunity, Mucosal; Mucous Membrane; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus; Vagina
PubMed: 23772612
DOI: 10.1111/imr.12072 -
Mucosal Immunology May 2008The mucosal tissues of the gastrointestinal, respiratory, reproductive, and urinary tracts, and the surface of the eye present an enormous surface area to the exterior... (Review)
Review
The mucosal tissues of the gastrointestinal, respiratory, reproductive, and urinary tracts, and the surface of the eye present an enormous surface area to the exterior environment. All of these tissues are covered with resident microbial flora, which vary considerably in composition and complexity. Mucosal tissues represent the site of infection or route of access for the majority of viruses, bacteria, yeast, protozoa, and multicellular parasites that cause human disease. Mucin glycoproteins are secreted in large quantities by mucosal epithelia, and cell surface mucins are a prominent feature of the apical glycocalyx of all mucosal epithelia. In this review, we highlight the central role played by mucins in accommodating the resident commensal flora and limiting infectious disease, interplay between underlying innate and adaptive immunity and mucins, and the strategies used by successful mucosal pathogens to subvert or avoid the mucin barrier, with a particular focus on bacteria.
Topics: Animals; Humans; Immunity, Active; Immunity, Innate; Immunity, Mucosal; Infections; Mucins; Mucous Membrane; Protein Conformation
PubMed: 19079178
DOI: 10.1038/mi.2008.5 -
Journal of Biotechnology Aug 1999Feline immunodeficiency virus (FIV) infection is a naturally occurring lentiviral infection of cats which progresses to immunodeficiency in a manner strikingly similar... (Review)
Review
Feline immunodeficiency virus (FIV) infection is a naturally occurring lentiviral infection of cats which progresses to immunodeficiency in a manner strikingly similar to that observed in HIV infection in man. The rectal and cervico-vaginal mucosae are common routes of transmission of HIV and it has been shown that the gastrointestinal tract is an important site of HIV infection and primary pathology. Although biting is the principle mode of transmission for FIV, we have shown that it is possible to reliably infect cats via both the rectal and vaginal routes. Using a biotin-streptavidin linked immunoperoxidase technique we have detected FIV core and envelope proteins in the colonic follicle associated epithelial cells, cells within the lymphoid follice and occasional cells in the lamina propria. Further, in the intestine we have detected FIV RNA and proviral DNA in epithelial cells, colonic lymphoid aggregates and isolated lamina propria cells. We have studied a group of asymptotic cats which have been rectally infected with FIV for 1 year or longer and shown an increase in the number of lamina propria CD8+ cells and greater levels of IL-2, IL-6, IL-10 and gamma-IFN mRNA. Since these cats remained clinically healthy these results might suggest that both local antibody and class I restricted cytotoxic lymphocytes (CTLs) may play a role in control of viral replication. We have investigated a range of vaccination regimes for their ability to generate responses which would protect from rectal challenge with virulent virus. Cats have been immunized with whole virus (FIV-pet, FIV-GLA-8), V3, V3MAP or C2 with cholera toxin (CT), or Quil A based adjuvants via rectal, intra-nasal, parenteral or targeted lymph node routes, and challenged rectally with ten mucosal cat infectious doses (MCID) of FIV-GLA-8. We have shown that the adjuvant effects of cholera toxin and Quil A are not influenced by the route of delivery (intraperitoneal (i.p.) versus rectal) with CT more effective in stimulating humoral and Quil A more effective in stimulating cellular responses to FIV antigens. However we have shown that, quantitatively, CT is more effective when used as an adjuvant via the intra-nasal than the rectal route. Recently, we have begun to investigate if the promising results obtained with targeted lymph node (TLN) vaccination in monkeys could be reproduced in the cat. We have shown that TLN was more effective than rectal immunisation in stimulating both humoral and proliferative responses. In a preliminary study we have also been able to detect FIV specific CTLs and have observed protection from rectal challenge in four out of four cats.
Topics: Animals; Biotechnology; Cats; Cytokines; Feline Acquired Immunodeficiency Syndrome; Female; Humans; Immunity, Mucosal; Immunodeficiency Virus, Feline; Mucous Membrane; Viral Vaccines
PubMed: 10486930
DOI: 10.1016/s0168-1656(99)00139-x -
Current Topics in Microbiology and... 2012Natural transmission of human immunodeficiency virus type 1 (HIV-1) occurs through gastrointestinal and vaginal mucosa. These mucosal tissues are major reservoirs for... (Review)
Review
Natural transmission of human immunodeficiency virus type 1 (HIV-1) occurs through gastrointestinal and vaginal mucosa. These mucosal tissues are major reservoirs for initial HIV replication and amplification, and the sites of rapid CD4(+) T cell depletion. In both HIV-infected humans and SIV-infected macaques, massive loss of CD4(+) CCR5(+) memory T cells occurs in the gut and vaginal mucosa within the first 10-14 days of infection. Induction of local HIV-specific immune responses by vaccines may facilitate effective control of HIV or SIV replication at these sites. Vaccines that induce mucosal responses, in particular CD8(+) cytotoxic T lymphocytes (CTL), have controlled viral replication at mucosal sites and curtailed systemic dissemination. Thus, there is strong justification for development of next generation vaccines that induce mucosal immune effectors against HIV-1 including CD8(+) CTL, CD4(+) T helper cells and secretory IgA. In addition, further understanding of local innate mechanisms that impact early viral replication will greatly inform future vaccine development. In this review, we examine the current knowledge concerning mucosal AIDS vaccine development. Moreover, we propose immunization strategies that may be able to elicit an effective immune response that can protect against AIDS as well as other mucosal infections.
Topics: AIDS Vaccines; Animals; HIV Infections; HIV-1; Humans; Immunity, Mucosal; Mucous Membrane
PubMed: 21203884
DOI: 10.1007/82_2010_119 -
Viruses Apr 2017Human papillomavirus (HPV)-induced neoplasms have long been considered to originate from viral infection of the basal cell layer of the squamous mucosa. However, this... (Review)
Review
Human papillomavirus (HPV)-induced neoplasms have long been considered to originate from viral infection of the basal cell layer of the squamous mucosa. However, this paradigm has been recently undermined by accumulating data supporting the critical role of a discrete population of squamo-columnar (SC) junction cells in the pathogenesis of cervical (pre)cancers. The present review summarizes the current knowledge on junctional cells, discusses their high vulnerability to HPV infection, and stresses the potential clinical/translational value of the novel dualistic model of HPV-related carcinogenesis.
Topics: Carcinogenesis; Epithelial Cells; Humans; Mucous Membrane; Papillomaviridae; Papillomavirus Infections
PubMed: 28425968
DOI: 10.3390/v9040085 -
Clinical & Developmental Immunology 2011Interactions between mucosal surfaces and microbial microbiota are key to host defense, health, and disease. These surfaces are exposed to high numbers of microbes and... (Review)
Review
Interactions between mucosal surfaces and microbial microbiota are key to host defense, health, and disease. These surfaces are exposed to high numbers of microbes and must be capable of distinguishing between those that are beneficial or avirulent and those that will invade and cause disease. Our understanding of the mechanisms involved in these discriminatory processes has recently begun to expand as new studies bring to light the importance of epithelial cells and novel immune cell subsets such as T(h)17 T cells in these processes. Elucidating how these mechanisms function will improve our understanding of many diverse diseases and improve our ability to treat patients suffering from these conditions. In our voyage to discover these mechanisms, mucosal interactions with opportunistic commensal organisms such as the fungus Candida albicans provide insights that are invaluable. Here, we review current knowledge of the interactions between C. albicans and epithelial surfaces and how this may shape our understanding of microbial-mucosal interactions.
Topics: Animals; Candida albicans; Candidiasis; Cytokines; Epithelial Cells; Humans; Immunity, Mucosal; Mucous Membrane; Signal Transduction
PubMed: 21776285
DOI: 10.1155/2011/346307 -
Immunology Letters Dec 2017We review the recent human mucosal-associated invariant T (MAIT) cell literature to examine the signals that control MAIT cell activation. We discuss these signals in... (Review)
Review
We review the recent human mucosal-associated invariant T (MAIT) cell literature to examine the signals that control MAIT cell activation. We discuss these signals in context of MAIT cell function in mucosal barrier tissues and address how MAIT cells avoid responding to commensal bacteria, while maintaining responsiveness to infections.
Topics: Animals; Bacterial Infections; Cytokines; Diagnosis, Differential; Homeostasis; Humans; Immune Tolerance; Immunity, Innate; Mucosal-Associated Invariant T Cells; Mucous Membrane
PubMed: 28987476
DOI: 10.1016/j.imlet.2017.09.013 -
Journal of the American Academy of... Feb 2015Mycoplasma pneumoniae infection is associated with extrapulmonary complications, including mucocutaneous eruptions. These eruptions, which have been termed either... (Review)
Review
BACKGROUND
Mycoplasma pneumoniae infection is associated with extrapulmonary complications, including mucocutaneous eruptions. These eruptions, which have been termed either "Stevens-Johnson syndrome" or "erythema multiforme" in the literature, may differ from drug-induced Stevens-Johnson syndrome or viral-associated erythema multiforme.
OBJECTIVE
We sought to review the literature characterizing morphology and disease course of M pneumoniae-associated mucocutaneous disease.
METHODS
A comprehensive literature search identified 95 articles with 202 cases.
RESULTS
Patients were often young (mean age: 11.9 years) and male (66%). Cutaneous involvement ranged from absent (34%), to sparse (47%), to moderate (19%). Oral, ocular, and urogenital mucositis was reported in 94%, 82%, and 63% of cases, respectively. Treatments included antibiotics (80%), systemic corticosteroids (35%), supportive care alone (8%), and/or intravenous immunoglobulin (8%). Complications included mucosal damage (10%), cutaneous scarring (5.6%), recurrence (8%), and mortality (3%).
LIMITATIONS
Mild cases may not have been published; thus this review may have a bias toward more severe disease.
CONCLUSION
M pneumoniae-associated mucocutaneous disease has prominent mucositis and sparse cutaneous involvement, although cutaneous involvement varies. Because of the distinct morphology, mild disease course, and potentially important clinical implications regarding treatment, we propose a revision of the nomenclature system and suggest the term "Mycoplasma-induced rash and mucositis" for these cases.
Topics: Adrenal Cortex Hormones; Age Distribution; Anti-Bacterial Agents; Child; Diagnosis, Differential; Erythema Multiforme; Exanthema; Female; Humans; Immunoglobulins, Intravenous; Male; Mucositis; Mycoplasma Infections; Mycoplasma pneumoniae; Sex Distribution; Stevens-Johnson Syndrome; Syndrome; Treatment Outcome
PubMed: 25592340
DOI: 10.1016/j.jaad.2014.06.026