Medicine and Health Sciences Commons^™

Sjl Mice Infected With Acanthamoeba Castellanii Develop Central Nervous System Autoimmunity Through The Generation Of Cross-Reactive T Cells For Myelin Antigens, Chandirasegaran Massilamany, Francine Marciano-Cabral, Bruno Da Rocha-Azevedo, Melissa Jamerson, Arunakumar Gangaplara, David Steffen, Rana Zabad, Zsolt Illes, Raymond A. Sobel, Jay Reddy

Microbiology and Immunology Publications

We recently reported that Acanthamoeba castellanii (ACA), an opportunistic pathogen of the central nervous system (CNS) possesses mimicry epitopes for proteolipid protein (PLP) 139–151 and myelin basic protein 89–101, and that the epitopes induce experimental autoimmune encephalomyelitis (EAE) in SJL mice reminiscent of the diseases induced with their corresponding cognate peptides. We now demonstrate that mice infected with ACA also show the generation of cross-reactive T cells, predominantly for PLP 139–151, as evaluated by T cell proliferation and IAs/dextramer staining. We verified that PLP 139–151-sensitized lymphocytes generated in infected mice contained a high proportion of T helper 1 cytokine-producing cells, …

Reduction Of The Hiv Protease Inhibitor-Induced Er Stress And Inflammatory Response By Raltegravir In Macrophages, Xiaoxuan Zhang, Risheng Cao, Ruping Liu, Renping Zhao, Yi Huang, Emily C. Gurley, Phillip B. Hylemon, William M. Pandak, Guangji Wang, Luyong Zhang, Xiaokun Li, Huiping Zhou

Microbiology and Immunology Publications

Background

HIV protease inhibitor (PI), the core component of highly active antiretroviral treatment (HAART) for HIV infection, has been implicated in HAART-associated cardiovascular complications. Our previous studies have demonstrated that activation of endoplasmic reticulum (ER) stress is linked to HIV PI-induced inflammation and foam cell formation in macrophages. Raltegravir is a first-in-its-class HIV integrase inhibitor, the newest class of anti-HIV agents. We have recently reported that raltegravir has less hepatic toxicity and could prevent HIV PI-induced dysregulation of hepatic lipid metabolism by inhibiting ER stress. However, little information is available as to whether raltegravir would also prevent HIV PI-induced inflammatory …

Phase Variation Of Poly-N-Acetylglucosamine Expression In Staphylococcus Aureus, Jamie L. Brooks, Kimberly K. Jefferson

Microbiology and Immunology Publications

Polysaccharide intercellular adhesin (PIA), also known as poly-N-acetyl-β-(1–6)-glucosamine (PIA/PNAG) is an important component of Staphylococcus aureus biofilms and also contributes to resistance to phagocytosis. The proteins IcaA, IcaD, IcaB, and IcaC are encoded within the intercellular adhesin (ica) operon and synthesize PIA/PNAG. We discovered a mechanism of phase variation in PIA/PNAG expression that appears to involve slipped-strand mispairing. The process is reversible and RecA-independent, and involves the expansion and contraction of a simple tetranucleotide tandem repeat within icaC. Inactivation of IcaC results in a PIA/PNAG-negative phenotype. A PIA/PNAG-hyperproducing strain gained a fitness advantage in vitro following the …

P. Aeruginosa Sgnh Hydrolase-Like Proteins Algj And Algx Have Similar Topology But Separate And Distinct Roles In Alginate Acetylation, Perrin Baker, Tyler Ricer, Patrick J. Moynihan, Elena N. Kitova, Marthe T. C. Walvoort, Dustin J. Little, John C. Whitney, Karen Dawson, Joel T. Weadge, Howard Robinson, Dennis E. Ohman, Jeroen D. C. Codee, John S. Klassen, Anthony J. Clarke, P. Lynne Howell

Microbiology and Immunology Publications

The O-acetylation of polysaccharides is a common modification used by pathogenic organisms to protect against external forces. Pseudomonas aeruginosa secretes the anionic, O-acetylated exopolysaccharide alginate during chronic infection in the lungs of cystic fibrosis patients to form the major constituent of a protective biofilm matrix. Four proteins have been implicated in the O-acetylation of alginate, AlgIJF and AlgX. To probe the biological function of AlgJ, we determined its structure to 1.83 Å resolution. AlgJ is a SGNH hydrolase-like protein, which while structurally similar to the N-terminal domain of AlgX exhibits a distinctly different electrostatic surface potential. Consistent with other SGNH …

Antigen Transfer From Exosomes To Dendritic Cells As An Explanation For The Immune Enhancement Seen By Ige Immune Complexes, Rebecca K. Martin, Keith B. Brooks, Frida Henningsson, Birgitta Heyman, Daniel H. Conrad

Microbiology and Immunology Publications

IgE antigen complexes induce increased specific T cell proliferation and increased specific IgG production. Immediately after immunization, CD23+ B cells capture IgE antigen complexes, transport them to the spleen where, via unknown mechanisms, dendritic cells capture the antigen and present it to T cells. CD23, the low affinity IgE receptor, binds IgE antigen complexes and internalizes them. In this study, we show that these complexes are processed onto B-cell derived exosomes (bexosomes) in a CD23 dependent manner. The bexosomes carry CD23, IgE and MHC II and stimulate antigen specific T-cell proliferation in vitro. When IgE antigen complex stimulated bexosomes …

Flavonoid Apigenin Inhibits Lipopolysaccharide-Induced Inflammatory Response Through Multiple Mechanisms In Macrophages, Xiaoxuan Zhang, Guangji Wang, Emily C. Gurley, Huiping Zhou

Microbiology and Immunology Publications

Background

Apigenin is a non-toxic natural flavonoid that is abundantly present in common fruits and vegetables. It has been reported that apigenin has various beneficial health effects such as anti-inflammation and chemoprevention. Multiple studies have shown that inflammation is an important risk factor for atherosclerosis, diabetes, sepsis, various liver diseases, and other metabolic diseases. Although it has been long realized that apigenin has anti-inflammatory activities, the underlying functional mechanisms are still not fully understood.

Methodology and Principal Findings

In the present study, we examined the effect of apigenin on LPS-induced inflammatory response and further elucidated the potential underlying mechanisms in …

Antigen Transfer From Exosomes To Dendritic Cells As An Explanation For The Immune Enhancement Seen By Ige Immune Complexes, Rebecca K. Martin, Keith B. Brooks, Frida Henningsson, Birgitta Heyman, Daniel H. Conrad

Microbiology and Immunology Publications

IgE antigen complexes induce increased specific T cell proliferation and increased specific IgG production. Immediately after immunization, CD23+ B cells capture IgE antigen complexes, transport them to the spleen where, via unknown mechanisms, dendritic cells capture the antigen and present it to T cells. CD23, the low affinity IgE receptor, binds IgE antigen complexes and internalizes them. In this study, we show that these complexes are processed onto B-cell derived exosomes (bexosomes) in a CD23 dependent manner. The bexosomes carry CD23, IgE and MHC II and stimulate antigen specific T-cell proliferation in vitro. When IgE antigen complex stimulated bexosomes …

An Emerging Mycoplasma Associated With Trichomoniasis, Vaginal Infection And Disease, Jennifer M. Fettweis, Myrna G. Serrano, Bernice Huang, J. Paul Brooks, Abigail L. Glascock, Nihar U. Sheth, Vaginal Microbiome Consortium, Jerome F. Strauss Iii, Kimberly K. Jefferson, Gregory A. Buck

Microbiology and Immunology Publications

Humans are colonized by thousands of bacterial species, but it is difficult to assess the metabolic and pathogenic potential of the majority of these because they have yet to be cultured. Here, we characterize an uncultivated vaginal mycoplasma tightly associated with trichomoniasis that was previously known by its 16S rRNA sequence as “Mnola.” In this study, the mycoplasma was found almost exclusively in women infected with the sexually transmitted pathogen Trichomonas vaginalis, but rarely observed in women with no diagnosed disease. The genomes of four strains of this species were reconstructed using metagenome sequencing and assembly of DNA from …

An Emerging Mycoplasma Associated With Trichomoniasis, Vaginal Infection And Disease, Jennifer M. Fettweis, Myrna G. Serrano, Bernice Huang, J. Paul Brooks, Abigail L. Glascock, Nihar U. Sheth, Vaginal Microbiome Consortium, Jerome F. Strauss Iii, Kimberly K. Jefferson, Gregory A. Buck

Microbiology and Immunology Publications

Humans are colonized by thousands of bacterial species, but it is difficult to assess the metabolic and pathogenic potential of the majority of these because they have yet to be cultured. Here, we characterize an uncultivated vaginal mycoplasma tightly associated with trichomoniasis that was previously known by its 16S rRNA sequence as “Mnola.” In this study, the mycoplasma was found almost exclusively in women infected with the sexually transmitted pathogen Trichomonas vaginalis, but rarely observed in women with no diagnosed disease. The genomes of four strains of this species were reconstructed using metagenome sequencing and assembly of DNA from four …

Evolution Of Our Understanding Of Myeloid Regulatory Cells: From Mdscs To Mregs, Masoud H. Manjili

Microbiology and Immunology Publications

The term myeloid-derived suppressor cells (MDSCs) was first suggested in 2007 in order to reflect the origin and function of myeloid cells during immunosuppression in cancer and other pathologic conditions. Emerging evidence suggests that MDSCs suppress CTL and Th1 responses in malignant diseases while they regulate effective immune responses in parasitic and helminth infections as well as Th17 inflammatory response during autoimmune diseases. Based on these data, the term myeloid regulatory cells (Mregs) more accurately reflects their function and interactions with different cells of the immune system during diseased conditions. Here, we provide evidence on the multifaceted function of Mregs …