These studies have established a role for antigen-specific, IgM-mediated protective effects against intracellular pathogens. by a wide array of sophisticated mechanisms to modulate and to evade the host immune response [5, 6]. A na?ve host develops primary tuberculosis upon the first encounter with [7]. Most of the infection is restricted and well contained at the primary site of bacterium-host interaction and the local draining lymph nodes, which together, are Zaurategrast (CDP323) called the Ghon complex [7]. It is generally accepted despite being well controlled, the bacilli are not eradicated due to the unique ability of to enter a dormant state to establish a clinically silent latent infection that can subsequently reactivate to Rabbit polyclonal to ACTR1A cause active diseases, sometimes decades later [8C10]. Post-primary tuberculosis, which occurs in a sensitized host, accounts for most of the cases that manifest active diseases, and is generally caused by exogenous reinfection or reactivation of latent bacilli [7]. The mechanisms underlying tuberculous reactivation remain to be clearly defined; but Zaurategrast (CDP323) it is well established that a host with compromised immune function, such as individuals with HIV infection and those receiving tumor necrosis factor (TNF) blockade therapy, is at increased risks for developing disease recrudescence [11C13]. The latently infected constitute a reservoir of individuals that is critical for the perpetuation of the Zaurategrast (CDP323) tubercle bacillus. These unique properties to persist in and transmit insidiously among the population render eradication of difficult [14]. In the post primary stage of infection, has the propensity to promote the development of caseating pneumonia in the sensitized host that can lead to tissue necrosis and eventual cavitation [7]. These immunopathological changes, whose underlying mechanisms have not been clearly characterized, enable effective bacterial transmission and therefore play an important role in the pathogenesis of the tubercle bacillus [7, 15]. A most effective way to combat an infectious disease is through immunization with efficacious vaccines [16]. For example, the existing measles vaccine costs approximately $17/disability-adjusted life year, making it one of the most cost-effective health interventions in developing countries [17]. The development of a reliable and effective vaccine against in the host [6], which elicits a spectrum of immunological responses not yet completely characterized; and the lack of a well-defined molecular and biochemical signature of protection against infection [19, 21]. The only anti-tuberculosis vaccine currently in use is bacillus Calmette-Gurin (BCG) [22]. Although this vaccine effectively protects against severe childhood tuberculosis, its efficacy against adult pulmonary disease is inconsistent [23C26]. Concerted efforts of the tuberculosis community, however, together with advances in the fields of immunology and vaccinology [17, 27, 28], should hold promise for the rational design of effective vaccines against [18C20]. Characterization of the immune response to has largely focused on cell-mediated immunity [18C20]. This approach is not without reasons. For example, the inconsistent efficacy of passive serum therapy in treating tuberculosis in the late nineteenth century, which was likely due to the use of non-standardized protocols and reagent, had cast doubt on the significance of humoral immunity in the control of [29, 30]. This Zaurategrast (CDP323) doubt has been further bolstered by the generally accepted concept that while cell-mediated immunity plays a critical role in defense against intracellular pathogens, their extracellular counterparts are best controlled by B cell and humoral immune response [31C33]. Based on this latter concept, vaccine development against intracellular pathogens, including will likely gain new insights that can help design anti-tuberculosis strategies, including immunotherapies and vaccines. The role of B cells and humoral immunity in regulating the immune response against intracellular pathogens Accumulating evidence suggest that the concept of division of immunological labor in host defense against intracellular and extracellular microbes, as discussed above, is not absolute. It is becoming clear that B cells and immunoglobulins contribute significantly to shaping the immune response to and/or engendering protection against pathogens such as and [37C50], whose life cycle includes a significant intracellular sojourn of varying extent. In fct, a conjugate vaccine has been made that protects against the intracellular pathogen by antibody-mediated immunity alone [51]. Of note, as obligatory an intracellular organism as Ehrlichia is [39] the life cycle of this bacterium has a transient extracellular phase that may lead to its susceptibility to the antimicrobial effects of antibodies that may be mediated through direct interaction between immunoglobulins and the target pathogen. This scenario is applicable to as emerging evidence support the notion that extracellular tubercle bacilli are likely not an uncommon entity in an infected host, particularly one (such as humans) in whom necrosis is part of the immunopathological process [52, 53]. Direct contact with target pathogens is, however, not requisite to the execution of the antimicrobial effects of antibodies. For example, certain contact-independent mechanisms against viruses, the quintessential intracellular pathogens, protect by attenuating viral transcription and replication via the binding of antibodies to specific antigens of the virion present on the membrane.