Anthrax toxin effects on B lymphocyte function

Bacillus anthracis is a gram-positive spore-forming rod capable of causing cutaneous, gastrointestinal and inhalational anthrax. It has a number of virulence factors of which, the two toxins are of great importance. Lethal toxin is a zinc metaloprotease that cleaves the N terminus of the mitogen-activated protein kinase (MAPK) kinase family 1-7, with the exception of MEK5. This kinase family is responsible for activating the mitogen-activated protein kinase (MAPK) cascade. This cascade includes extracellular signal-regulated protein kinases (ERK), c-Jun NH2-terminal kinases (JNK) and p38 kinases. The disruption of these signaling pathways has a number of deleterious downstream effects that vary by cell type. Edema factor is a powerful calmodulin-dependent adenylyl cyclase that forms 3’,5’-adenosine monophosphate (cAMP) from adenosine triphosphate (ATP). This enzymatic reaction causes an increase in intracellular cyclic AMP (cAMP) in host cells. As cAMP is a prominent second messenger in cellular signaling, edema toxin has a wide array of effects on numerous cell types and functions. \r\nTo determine the effects of the anthrax toxins on the adaptive immune response, B lymphocytes were exposed to LeTx or EdTx in vitro. LeTx and EdTx both inhibit B cell activation in different manners. LeTx inhibited B cell proliferation but not migration, while EdTx inhibited B cell migration but not proliferation. LeTx and EdTx altered expression patterns of B cell activation markers. EdTx inhibited MIP-1α and MIP-1β while enhancing IL-6 production. Previously unseen in any cell type EdTx was demonstrated to be cytotoxic to naïve B cells.\r\nThe research presented in this report illustrates the inhibitory effects of LeTx and EdTx on B lymphocytes, providing valuable insight into the immunoevasion tactics of B. anthracis.\r\n

Name thesis:degree_name

PhD

Level thesis:degree_level

Doctoral

Grantor

The University of Texas Medical Branch

Year dc:date.issued

2010

Author dc:creator

• Bryan Thomas Gnade

Advisor dc:contributor.advisor

• Johnny Peterson

Committee members dc:contributor.committeemember

• Rolf Konig
• Gustavo Valbuena
• David Craft

• lethal toxin
• edema toxin
• bacillus anthracis
• B cell
• anthrax toxin
• anthrax

Statement dc:rights

• Copyright © is held by the author. Presentation of this material on the TDL web site by The University of Texas Medical Branch at Galveston was made possible under a limited license grant from the author who has retained all copyrights in the works.

Language dc:language.iso

eng

Dc Identifier Other

etd-03112010-180727

OAI identifier oai:identifier

oai:utmb-ir.tdl.org:2152.3/40