PRODUCT ORIGIN/DESCRIPTION Dect<strong>in</strong>-1 Agonists Curdlan NEW Beta-1,3-glucan from Alcaligenes faecalis
INNATE IMMUNITY 3 TLR2 Agonists FSL-1 - TLR2/6 Agonist FSL-1 (Pam2CGDPKHPKSF) is a synthetic lipoprote<strong>in</strong> derived from Mycoplasma salivarium similar to MALP-2, a M. fermentans derived lipopeptide (LP) 1,2 . Mycoplasmal LPs, such as FSL-1, conta<strong>in</strong> a diacylated cyste<strong>in</strong>e residue, whereas bacterial LP conta<strong>in</strong> a triacylated one. FSL-1 is recognized by TLR2 and TLR6, whereas bacterial LPs are recognized by TLR2 and TLR1 3 . HKAL (Acholeplasma laidlawii) Acholeplasma laidlawii, a member of the mycoplasma family, is a cell wall-less bacteria. Heat killed mycoplasma such as HKAL <strong>in</strong>duce higher stimulation of macrophage than lipoprote<strong>in</strong>s from Gram- bacteria, even at low concentrations 4 . This response is mediated by TLR2 and MyD88. HKEB (Escherichia coli) NEW HKEB is a heat killed preparation of the gram negative bacterium, E.coli O111:B4. Cell wall components from this bacterium, such as peptidoglycan (PGN) and lipopolysaccharide (LPS), are recognized by TLR2 and TLR4 5 . It has been demonstrated that HKEB can stimulate TLR2 and <strong>in</strong>duce the production of NF-kB and pro-<strong>in</strong>flammatory cytok<strong>in</strong>es, such as IL-8 6 . HKEB is a potent stimulator of TLR2, and has a weak stimulatory effect on TLR4. HKHP (Helicobacter pylori) Helicobacter pylori, a Gram negative bacterium, is an important human pathogen that causes gastritis and is strongly associated with peptic ulcer, gastric adenocarc<strong>in</strong>oma, and mucosa-associated lymphoid tissue lymphoma. Heat-killed Helicobacter pylori (HKHP) <strong>in</strong>duces the production of IL-8 through the activation of the ERK and p38 MAPK pathway. TLR2 was shown to be the sensor <strong>in</strong>volved <strong>in</strong> HKHP-mediated secretion of IL-8 <strong>in</strong> monocytes 7 . HKLM (Listeria monocytogenes) HKLM is a freeze-dried heat-killed preparation of Listeria monocytogenes (LM), a facultative <strong>in</strong>tracellular Gram-positive bacterium. Infection with LM <strong>in</strong>duces the secretion of <strong>in</strong>flammatory cytok<strong>in</strong>es, such as TNF, IL-12, and several chemok<strong>in</strong>es, allow<strong>in</strong>g the recruitment and activation of immune cells. This response is mediated ma<strong>in</strong>ly by the <strong>in</strong>teraction between MyD88 and TLR2 8, 9 . HKLP (Legionella pneumophila) Legionella pneumophila, a Gram negative bacterium, is the causative agent of legionnaires’ disease which is characterized by severe pneumonia. Although TLR4 is <strong>in</strong>volved <strong>in</strong> host defense aga<strong>in</strong>st gram negative bacteria <strong>in</strong>fection, it is not activated or is activated only to a limited extent by L. pneumophila 10 . L. pneumophila requires TLR2 rather than TLR4 to <strong>in</strong>duce the production of cytok<strong>in</strong>es 11 . HKLR (Lactobacillus rhamnosus) Lactobacillus rhamnosus is a nonpathogenic gram-positive <strong>in</strong>habitant of the human microflora. It is used as a natural preservative <strong>in</strong> yogurt and other dairy products to extend the shelf life. L. rhamnosus is known to have health beneficial effects, such as the nonspecific enhancement of the immune system. Indeed, heat-killed L.. rhamnosus (HKLR) has been shown to be a potent <strong>in</strong>ducer of TNF-a from mouse mononuclear cells. This immune response is dependent on TLR2 and CD14 12 . HKMF (Mycoplasma fermentans) NEW Mycoplasma fermentans, a member of the mycoplasma family, is a cell wall-less bacterium. It conta<strong>in</strong>s lipopeptides, <strong>in</strong> particular 2-kDa macrophage-activat<strong>in</strong>g lipopetide (MALP-2), a potent stimulator of macrophages through TLR2 and TLR6 3 . Stimulation with heat killed M. fermentans (HKMF) <strong>in</strong>duces rapid activation of NF-kB and the production of pro-<strong>in</strong>flammatory cytok<strong>in</strong>es. HKPA (Pseudomonas aerug<strong>in</strong>osa) Pseudomonas aerug<strong>in</strong>osa is a virulent gram-negative pathogen that <strong>in</strong>fects patients through the respiratory tract, <strong>in</strong> particular patients with cystic fibrosis. Heat-killed Pseudomonas aerug<strong>in</strong>osa (HKPA) <strong>in</strong>itiates host <strong>in</strong>flammatory responses through TLR2 and TLR5 but not TLR4 13, 14 . The TLR5-mediated response was shown to be <strong>in</strong>duced by flagell<strong>in</strong> while LPS appears to play an important role <strong>in</strong> the TLR2-mediated response. HKPG (Porphyromonas g<strong>in</strong>givalis) HKPG is a freeze-dried heat-killed preparation of the periodontopathic Gram negative bacteria Porphyromonas g<strong>in</strong>givalis. In CHO cells express<strong>in</strong>g TLR2 and CD14, exposure to HKPG <strong>in</strong>duces the activation of NF-kB through TLR2. Expression of TLR4 fails to enhance the response to HKPG suggest<strong>in</strong>g that either the whole bacterial components of P. g<strong>in</strong>givalis are not recognized by TLR4 or some components of these bacteria <strong>in</strong>hibit TLR4-mediated activation 15 . HKSA (Staphylococcus aureus) HKSA is a lyophilized heat-killed preparation of Staphyloccocus aureus, a Gram-positive extra-cellular grow<strong>in</strong>g bacterium. HKSA is recognized ma<strong>in</strong>ly by TLR2 16 . HKSA <strong>in</strong>duces tolerance to a secondary HKSA stimulation but causes prim<strong>in</strong>g to LPS, suggest<strong>in</strong>g a differential regulation of cytok<strong>in</strong>es and chemok<strong>in</strong>es <strong>in</strong> gram-positive- and gram-negative-<strong>in</strong>duced <strong>in</strong>flammatory events 17 . HKSP (Streptococcus pneumoniae) Streptococcus pneumoniae, a Gram positive bacterium, is the pr<strong>in</strong>cipal etiologic agent of bacterial men<strong>in</strong>gitis <strong>in</strong> adults. Heat-killed Streptococcus pneumoniae (HKSP) <strong>in</strong>duce activation of NF-kB <strong>in</strong> a TLR2- and CD14-dependent manner 18 . TLR2 has been shown to play an important role <strong>in</strong> the prote<strong>in</strong>- and polysaccharide-specific type 1 IgG isotype response follow<strong>in</strong>g immunization with HKSP 19 . LM-MS & LAM-MS (Mycobacterium smegmatis) Lipoarab<strong>in</strong>omannans (LAM) and lipomannans (LM) are lipoglycans found <strong>in</strong> mycobacterial cell wall. LM and LAM from the non-pathogenic Mycobacterium smegmatis are pro<strong>in</strong>flammatory molecules 20 . Both LM-MS and LAM-MS activate macrophages <strong>in</strong> a TLR2-dependent manner 21 . 82 www.<strong>in</strong>vivogen.com/<strong>in</strong>nate-immunity-pamps
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