Recent clinical trials have established B cell depletion by the anti-CD20 chimeric antibody Rituximab as a beneficial therapy for patients with relapsing-remitting multiple sclerosis (MS). The impact of Rituximab on T cell responses remains largely unexplored. In the experimental autoimmune encephalomyelitis (EAE) model of MS in mice that express human CD20, Rituximab administration rapidly depleted peripheral B cells and strongly reduced EAE severity. B cell depletion was also associated with diminished Delayed Type Hypersensitivity (DTH) and a reduction in T cell proliferation and IL-17 production during recall immune response experiments. While Rituximab is not considered a broad immunosuppressant, our results indicate a role for B cells as a therapeutic cellular target in regulating encephalitogenic T cell responses in specific tissues.

The opportunistic pathogen Mycobacterium avium is a significant inhabitant of biofilms in drinking water distribution systems. M. avium expresses on its cell surface serovar-specific glycopeptidolipids (ssGPLs). Studies have implicated the core GPL in biofilm formation by M. avium and by other Mycobacterium species. In order to test this hypothesis in a directed fashion, three model systems were used to examine biofilm formation by mutants of M. avium with transposon insertions into pstAB (also known as nrp and mps). pstAB encodes the nonribosomal peptide synthetase that catalyzes the synthesis of the core GPL. The mutants did not adhere to polyvinyl chloride plates; however, they adhered well to plastic and glass chamber slide surfaces, albeit with different morphologies from the parent strain. In a model that quantified surface adherence under recirculating water, wild-type and pstAB mutant cells accumulated on stainless steel surfaces in equal numbers. Unexpectedly, pstAB mutant cells were >10-fold less abundant in the recirculating-water phase than parent strain cells. These observations show that GPLs are directly or indirectly required for colonization of some, but by no means all, surfaces. Under some conditions, GPLs may play an entirely different role by facilitating the survival or dispersal of nonadherent M. avium cells in circulating water. Such a function could contribute to waterborne M. avium infection.Members of the Mycobacterium avium complex (MAC), a group of closely related species and subspecies, are commonly isolated from water, food, soil, plants, and other samples. MAC species are associated with disease in birds and mammals, and some cause disease in susceptible humans. Sources of exposure include drinking water, spas, and soil. Mycobacteria are significant inhabitants of biofilms in these environments. They have been found in biofilm samples taken from water distribution systems, dental units, and medical devices at frequencies ranging from 69% to 95% of samples tested (1,11,12,25). Among the largest studies of mycobacteria in biofilms was that of Falkinham et al. (11). They sampled biofilms from posttreatment water pipes and customer water meters in eight U.S. cities. Mycobacteria were recovered from 69% of the samples and 100% of the sites. Slow-growing mycobacteria accounted for Ͼ90% of biofilm isolates. MAC species were the most common group recovered, accounting for 135 of the 267 (51%) individual Mycobacterium isolates from biofilm samples. In laboratory experiments, biofilm formation by MAC species has been correlated with chlorine resistance (24) and enhanced bronchial epithelial cell invasion (26). Despite its potential significance for human health, little is known about biofilm formation by the MAC.The cell walls of some Mycobacterium species have glycopeptidolipids (GPLs) that share a lipotetrapeptide core consisting of fatty acyl-NH-D-phenylalanine-D-allothreonine-D-alanine-L-alaninol (7). The alaninyl C terminus is rhamnosylated, and the allothreonine residue is linked to a...

Each year malaria kills hundreds of thousands of people and infects hundreds of millions of people despite current control measures. An effective malaria vaccine will likely be necessary to aid in malaria eradication. Vaccination using whole sporozoites provides an increased repertoire of immunogens compared to subunit vaccines across at least two life cycle stages of the parasite, the extracellular sporozoite, and intracellular liver stage. Three potential whole sporozoite vaccine approaches are under development and include genetically attenuated parasites, radiation attenuated sporozoites, and wild-type sporozoites administered in combination with chemoprophylaxis. Pre-clinical and clinical studies have demonstrated whole sporozoite vaccine immunogenicity, including humoral and cellular immunity and a range of vaccine efficacy that depends on the pre-exposure of vaccinated individuals. While whole sporozoite vaccines can provide protection against malaria in some cases, more recent studies in malaria-endemic regions demonstrate the need for improvements. Moreover, challenges remain in manufacturing large quantities of sporozoites for vaccine commercialization. A promising solution to the whole sporozoite manufacturing challenge is in vitro culturing methodology, which has been described for several Plasmodium species, including the major disease-causing human malaria parasite, Plasmodium falciparum. Here, we review whole sporozoite vaccine immunogenicity and in vitro culturing platforms for sporozoite production.

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