Innate immune response in Drosophila is mediated by signaling through Toll receptors. In mammals, Toll-like receptors (TLRs), comprising a large family, recognize a specific pattern of microbial components. So far, the roles of TLR2, TLR4, TLR5, TLR6, and TuR9 have been revealed. The recognition of microbial components by TLRs leads to activation of innate immunity, which provokes inflammatory responses and finally the development of adaptive immunity. The inflammatory response depends on a TLR-mediated MyD88-dependent cascade. However, there seems to exist additional cascades in TLR signaling. ln the case of TLR4 signaling, an MyD88-independent pathway is now being characterized. In addition to the activation of innate immune responses, TLR-mediated signaling leads to suppression of the activity of innate immune cells, represented by "lipopolysaccharide (LPS) tolerance". Progress in elucidating the molecular mechanisms for LPS tolerance has been made through the analysis of TLR-mediated signaling pathways. Thus, the activity for innate immune responses is known to be finely regulated by TLRs.

Recognition of bacterial envelope constituents is one mechanism used by mammalian cells to initiate responses leading to bacterial killing, or, unfortunately, responses that also cause fatal septic shock. Many cell surface receptors by which these microbial components are recognized have been identified and characterized over the past a few years. In addition to CD14, which has been shown to be involved in the recognition of many microbial components, Toll-like receptors and MD-2 have been identified as factors playing a role in the receptor complexes of these components. Here we review the recent findings regarding the molecular basis for the recognition of microbial components.

Recently, the clinical features of non-specific interstitial pneumonia (NSIP) have been described. We hypothesize that recurrent infection caused by Chlamydia pneumoniae may play a role in the pathogenesis of NSIP. To prove this, we quantified serum IgA and IgG antibodies against C. pneumoniae using the enzyme linked-immunosorbent assay kit. The study included 15 patients diagnosed with NSIP, 20 patients with chronic obstructive pulmonary diseases (COPD) as disease group, and 27 control subjects. IgA antibody against C. pneumoniae was positive in 12 of 15 patients with NSIP, in 16 of 20 patients with COPD, and in 14 of 27 control subjects. IgG antibody against C. pneumoniae was positive in 14 of 15 patients with NSIP, in 17 of 20 patients with COPD, and in 16 of 27 control subjects. If the cut off value (mean ± 2SD, index more than 3.0) was introduced, IgA and/or IgG antibodies against C. pneumoniae were positive in 8 of 15 patients with NSIP (53.3%), in 9 of 20 patients with COPD (45%), and in 2 of 27 control subjects (7.4%). These results suggest that infection of C. pneumoniae might play a role in the pathogenesis of NSIP.

Sixty-six clinical isolates of Candida albicans representing 14 different strain types were tested for their phospholipase and proteinase activities in correlation with adherence to buccal epithelial cells (BECs) and lethality to mice. Variations in phospholipase and proteinase production as well as adherence to BECs were observed both among isolates of the same strain type and between isolates of different strain types. All isolates tested, irrespective of strain type, produced low levels of phospholipase (0.5 mm for strain -BCD- and 2.7 mm for strain ABC--) and acid proteinase (0.6 mm for strain A --- E and 2.2 mm for strain --C--). A correlation was noted between adherence, phospholipase and proteinase production, and lethality to mice. C. albicans isolates, which adhered most strongly to BECs, exhibited higher levels of phospholipase and proteinase activities as well as higher pathogenicity. This was most evident in strain type --C--, which exhibited higher adherence ability (mean 717 ± 21 yeasts/100 BEC), and proteinase activity (mean 2.2 mm), and relatively higher phospholipase activity (mean 2.4 mm) compared with those of other strains. Additionally, this type was more prevalent and showed significantly higher levels of tissue colonization in the liver, kidneys, and spleen compared with most other strain types in both subjects with healthy dentates and complete denture wearers. These results clearly demonstrate the significant role of phospholipase and proteinase activities on the adherence of C. albicans and their overall influence on the pathogenesis of Candida species.

Typhoid is a global problem. Conventional diagnostic methods have limitations. The Widal test gives a high proportion of false positive results, and indiscriminate use of antibiotics has reduced the utility of blood culture. Consequently, these procedures are inadequate for diagnosing suspected cases of typhoid that do not present clear-cut symptoms. We previously showed that PCR-based diagnosis of typhoid targeting the flagellin gene has unparalleled specificity. We assessed the utility of this method for diagnosis of problematic cases of typhoid. A comparative study of PCR, blood culture, and Widal test was carried out on 55 cases of suspected typhoid with fever for 3-30 days and possessing an ambiguous clinical picture. A control group comprised of 20 healthy persons was also included. The respective positive results by PCR, blood culture, and Widal test for these groups were 58.2 and 0%, 14.5 and 0%, and 52.7 and 45%. Sensitivity of PCR as compared with that of blood culture was significantly better. We concluded that PCR is much superior to conventional methods and, due to its high sensitivity and specificity, can be of great use for rapid and definitive diagnosis of problematic cases of typhoid.