Characterization of NLRP12 during the In Vivo Host Immune Response to Klebsiella pneumoniae and Mycobacterium tuberculosis

The majority of nucleotide binding domain leucine rich repeats-containing (NLR) family members has yet to be functionally characterized. Of the described NLRs, most are considered to be proinflammatory and facilitate IL-1β production. However, a newly defined sub-group of NLRs that function as negative regulators of inflammation have been identified based on their abilities to attenuate NF-κB signaling. NLRP12 (Monarch-1) is a prototypical member of this sub-group that negatively regulates both canonical and noncanonical NF-κB signaling in biochemical assays and in colitis and colon cancer models. The role of NLRP12 in infectious diseases has not been extensively studied. Here, we characterized the innate immune response of Nlrp12(−/−) mice following airway exposure to LPS, Klebsiella pneumoniae and Mycobacterium tuberculosis. In response to E. coli LPS, Nlrp12(−/−) mice showed a slight decrease in IL-1β and increase in IL-6 production, but these levels were not statistically significant. During K. pneumoniae infection, we observed subtle differences in cytokine levels and significantly reduced numbers of monocytes and lymphocytes in Nlrp12(−/−) mice. However, the physiological relevance of these findings is unclear as no overt differences in the development of lung disease were observed in the Nlrp12(−/−) mice. Likewise, Nlrp12(−/−) mice demonstrated pathologies similar to those observed in the wild type mice following M. tuberculosis infection. Together, these data suggest that NLRP12 does not significantly contribute to the in vivo host innate immune response to LPS stimulation, Klebsiella pneumonia infection or Mycobacterium tuberculosis

Brucella: potential biothreat agent

Brucellosis is an ancient disease caused by brucellae, which are small, facultative, intracellular, gram-negative coccobacilli. Ten species of Brucella have been identified as the causative agents of brucellosis in mammalian hosts. Natural infections with Brucellae occur globally among humans and animals, resulting in significant economic losses. Research in recent years has focused on appropriate methods for environmental sampling, early detection techniques, decontamination procedures, and the development of new therapeutics and vaccines. Despite this research focus, there is still no human vaccine available. This is of particular concern as Brucellae are highly infectious via the aerosol route; therefore, they have the potential to be misused as agents of biological warfare. The global biological terrorist risk is increasing yearly due to a number of factors including increased migration, escalating numbers of displaced people, the speed and scale of global travel, and technological advances which have enhanced our ability to manipulate pathogens. Presented are a review of the recent developments in brucellosis research and an evaluation of the risks associated with the use of brucellae in deliberate biological attacks