IRAK-4 (interleukin-1 receptor-associated kinase 4), in the IRAK family, is a protein kinase involved in signaling innate immune responses from Toll-like receptors. It also supports signaling from T-cell receptors. IRAK4 contains domain structures which are similar to those of IRAK1, IRAK2, IRAKM and Pelle. IRAK4 is unique compared to IRAK1, IRAK2 and IRAKM in that it functions upstream of the other IRAKs, but is more similar to Pelle in this trait. IRAK4 has important clinical applications. Animals without IRAK-4 are more susceptible to viruses and bacteria but completely resistant to LPS challenge. History
The first IL-1 receptor-associated kinase (IRAK) was observed in 1994 through experiments with murine T helper cell lines D10N and EL-4. Two years later the first experimental member of this family of kinases, IRAK1, was cloned. In 2002, through database searches at the National Center for Biotechnology Information in an attempt to recognize novel members of the IRAK family, a human cDNA sequence which encoded a peptide sharing significant homology with IRAK1 was identified. This cDNA sequence was found to have five amino acid substitutions compared to IRAK1 and was termed IRAK4.IRAK4 was proposed to be the mammalian homolog of the Pelle gene found in Drosophila melanogaster and was proposed to require its kinase activity in order for it to function in activating NF-κB. It was also proposed by Li et al. that it might function upstream of other IRAKs and possibly cause a cascade of phosphorylation events through its function as an IRAK1 kinase.
The incubation period for the bacteria generally lasts from three-ten days. As the disease progresses. almost half the patients experience migratory polyarthralgias. Mechanism
Although the specific form of pathogenesis is still a subject of ongoing research, the bacteria has been observed to result in morphological symptoms that are atypical of bacterial infection. Autopsy of the victims vividly exhibit erythrophagocytosis, hepatosplenomegaly, interstitial pneumonia, and lymph node sinus hyperplasia. In addition, Myocarditis and Endocarditis have also been demonstrated in such patients. Synovial and serosal surfaces may be more suited for the growth of the bacteria within the body. Furthermore, leukocytoclastic vasculitis has been observed in the skin lesions. Diagnosis
The microaerophilic conditions needed for the bacteria to grow, makes its detection incredibly difficult. Trypticase soy agar or broth enriched with 20% blood, serum, or ascitic fluid is necessary for the optimal growth of the bacteria under laboratory conditions. The organism may take up to seven days to grow and the colonies generally have a circular, grayish and shiny appearance on agar. Once the microbe has grown, primary identification can be carried out via biochemical and carbohydrate fermentation analysis. Biochemical tests such as oxidase, catalase, indole, and nitrate can be used to detect the bacteria. However, S. moniliformis can be biochemically differentiated from similar bacteria by their negative production of indole, catalase, and oxidase, while reduction of nitrate to nitrite. PCR assay specific for Streptobacillus moniliformis can also be used to detect the bacteria in a patient sample with high accuracy.