Upon infection, pathogen and host compete for the same iron pool, because this trace metal is a crucial micronutrient for all living cells. Iron dysregulation in the host is strongly associated with poor outcomes in several infectious diseases, including tuberculosis, AIDS, and malaria, and inefficient iron scavenging by pathogens severely affects their virulence. Hepcidin is the master regulator of iron homeostasis in vertebrates, responsible for diminishing iron export from macrophages during iron overload or infection.
View Article and Find Full Text PDFE26 Transformation specific (Ets) family transcription factors control the expression of a large number of genes regulating hematopoietic cell development and function. Two such transcription factors, Ets-1 and myeloid Elf-1-like factor (MEF), have been shown to play critical roles in both natural killer (NK)- and NKT-cell development, but not in the development of conventional T cells. In this study, we address the role of E74-like factor 1 (Elf-1), another Ets family transcription factor that is closely related to MEF but divergent from Ets-1, in NK- and NKT-cell development using Elf-1-deficient (Elf-1(-/-)) mice.
View Article and Find Full Text PDFExosomes are small 30-100 nm membrane vesicles released from hematopoietic and nonhematopoietic cells and function to promote intercellular communication. They are generated through fusion of multivesicular bodies with the plasma membrane and release of interluminal vesicles. Previous studies from our laboratory demonstrated that macrophages infected with Mycobacterium release exosomes that promote activation of both innate and acquired immune responses; however, the components present in exosomes inducing these host responses were not defined.
View Article and Find Full Text PDFThis study was designed to evaluate the immunotherapeutic potential of Mycobacterium tuberculosis Ag85AB emulsified with unmethylated CpG motif-containing oligonucleotide (CpG-ODN) and dimethyldioctadecylammonium bromide (DDA) adjuvants (Ag85AB-CpG-DDA) in conjunction with antituberculous drugs. Ag85 complex proteins of M. tuberculosis purified from total culture filtrate and purified proteins were emulsified with CpG-ODN and DDA adjuvants.
View Article and Find Full Text PDFBackground: Tuberculosis (TB), an infirmity that mainly affects the respiratory system, is the world's second deadliest infectious disease, with > 9 million new cases diagnosed in 2006. One-third of the world's population is now infected with the TB bacillus. According to the WHO, an estimated 1.
View Article and Find Full Text PDFActivation of both CD4(+) and CD8(+) T cells is required for an effective immune response to an M. tuberculosis infection. However, infected macrophages are poor antigen presenting cells and may be spatially separated from recruited T cells, thus limiting antigen presentation within a granuloma.
View Article and Find Full Text PDFThis study examined the role of intranasal vaccination with Mycobacterium tuberculosis antigen85 complex proteins formulated in dimethyldioctadecylammonium bromide against airway Mycobacterium tuberculosis challenge in mice. Intranasal vaccination with antigen85A and antigen85B induced a significantly higher level of interferon-gamma, interleukin-12 and interleukin-4 in cervical lymph nodes together with IgA and IgG, predominantly IgG2a isotype in nasal secretion over subcutaneous vaccination. Further, intranasal vaccination with antigen85A and antigen85B imparted protection comparable with that obtained from intranasal or subcutaneous Mycobacterium bovis bacillus Calmette-Guerin immunization.
View Article and Find Full Text PDFThe effect of route of immunization on the protective efficacy of BCG against tuberculosis has been investigated. Immunoprotection was monitored by evaluating the bacterial burden in the lungs and spleen of mice challenged with Mycobacterium tuberculosis H(37)Rv after BCG immunization by intranasal (i.n.
View Article and Find Full Text PDFActivation of mucosal immunity in the respiratory tract is crucial for protection against respiratory infections. Whether the intranasal route of vaccination imparts better protection against pulmonary tuberculosis than that of subcutaneous vaccination remains a debatable issue. In this study, we have investigated the effect of the routes of immunization on the induction of immunoprotection against experimental tuberculosis employing mycobacterial culture filtrate proteins complexed with dimethyldioctadecylammonium bromide.
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