Scientific Publications by FDA Staff
Infect Immun 2013 Feb;81(2):585-97
IL-6 is essential for primary resistance to Francisella tularensis LVS infection.
Kurtz S, Foreman O, Bosio CM, Anver MR, Elkins KL
We employed Francisella tularensis LVS to study mechanisms of protective immunity against intracellular pathogens, and specifically to understand protective correlates. One potential molecular correlate identified previously was IL-6, a cytokine with pleotropic roles in immunity including influences on T and B cell functions. Given its role as an immune modulator and correlation with successful anti-LVS vaccination, we examined the role IL-6 plays in host response to LVS. IL-6 deficient (IL-6 KO) mice infected with LVS intradermally or intranasally, or anti-IL-6 treated mice, showed greatly reduced LD(50)s compared to wild type (WT) mice. Increased susceptibility was not due to altered splenic immune cell populations during infection or decreased serum antibody production, as IL-6 KO mice had similar compositions of each compared to WT mice. Although LVS-infected IL-6 KO produced much less serum amyloid A and haptoglobin (two acute phase proteins) compared to WT mice, there were no other obvious pathophysiological differences between LVS-infected WT and IL-6 KO mice. IL-6 KO or WT mice that survived primary LVS infection also survived a high dose LVS secondary challenge. Using an in vitro overlay assay that measures T cell activation, cytokine production, and abilities of the primed splenocytes to control intracellular LVS growth, we found that IL-6 KO total splenocytes or purified T cells were slightly defective in controlling intracellular LVS growth, but were equivalent in cytokine production. Taken together, IL-6 is an integral part of a successful immune response to primary LVS infection, but its exact role in precipitating adaptive immunity remains elusive.
|Category: Journal Article|
|PubMed ID: #23230288||DOI: 10.1128/IAI.01249-12|
|Includes FDA Authors from Scientific Area(s): Biologics|
|Entry Created: 2012-06-06||Entry Last Modified: 2013-04-21|