The lipopolysaccharide is the major component of Gram-negative bacteria outer membrane. LPS comprises three covalently linked regions: the lipid A, the rough core oligosaccharide, and the O-antigenic side chain determining serotype specificity. Wild-type LPS (sLPS) contains the O-antigenic side chain and is referred to as smooth. Rough LPS (rLPS) does not contain the O-side chain. Most wt bacteria and especially wt Enterobacteriaceae express prevalently the sLPS form although some truncated rLPS molecules always reach the external membrane. The two sLPS and rLPS forms are used almost indistinctly to study the effects on innate immune cells. Nevertheless, there is evidence that their mechanism of action may be different. For instance, while sLPS requires CD14 for the initiation of both MyD88-dependent and independent signal transduction pathways at least at low doses, rLPS leads to MyD88-dependent responses in the absence of CD14 even at low doses. Here we have identified additional differences in the signaling capacity of the two LPS species in the mouse. We have found that rLPS, diversely from sLPS, is capable of activating in dendritic cells (DCs) the Ca 2+/calcineurin and NFAT pathway in a CD14-independent manner, moreover it is also capable per se of activating the inflammasome and eliciting IL-1β secretion independent of the presence of additional stimuli required instead for sLPS. The ability of rLPS of activating the inflammasome in vitro has as a direct consequence a higher efficiency of rLPS-exposed DCs in activating natural killer (NK) cells compared to sLPS-exposed DCs. However, diversely from possible predictions, we found that the different efficiencies of the two LPS species in eliciting innate responses are almost nullified in vivo. Therefore, sLPS and rLPS induce nearly similar in vivo innate responses but with different mechanisms of signaling. © 2011 Elsevier B.V.

Zanoni, I., Bodio, C., Broggi, A., Ostuni, R., Caccia, M., Collini, M., et al. (2012). Similarities and differences of innate immune responses elicited by smooth and rough LPS. IMMUNOLOGY LETTERS, 142(1-2), 41-47 [10.1016/j.imlet.2011.12.002].

Similarities and differences of innate immune responses elicited by smooth and rough LPS

ZANONI, IVAN
Primo
;
BODIO, CATERINA
Secondo
;
BROGGI, ACHILLE;OSTUNI, RENATO;CACCIA, MICHELE;COLLINI, MADDALENA;VENKATESH, APARNA;SPREAFICO, ROBERTO;GRANUCCI, FRANCESCA
2012

Abstract

The lipopolysaccharide is the major component of Gram-negative bacteria outer membrane. LPS comprises three covalently linked regions: the lipid A, the rough core oligosaccharide, and the O-antigenic side chain determining serotype specificity. Wild-type LPS (sLPS) contains the O-antigenic side chain and is referred to as smooth. Rough LPS (rLPS) does not contain the O-side chain. Most wt bacteria and especially wt Enterobacteriaceae express prevalently the sLPS form although some truncated rLPS molecules always reach the external membrane. The two sLPS and rLPS forms are used almost indistinctly to study the effects on innate immune cells. Nevertheless, there is evidence that their mechanism of action may be different. For instance, while sLPS requires CD14 for the initiation of both MyD88-dependent and independent signal transduction pathways at least at low doses, rLPS leads to MyD88-dependent responses in the absence of CD14 even at low doses. Here we have identified additional differences in the signaling capacity of the two LPS species in the mouse. We have found that rLPS, diversely from sLPS, is capable of activating in dendritic cells (DCs) the Ca 2+/calcineurin and NFAT pathway in a CD14-independent manner, moreover it is also capable per se of activating the inflammasome and eliciting IL-1β secretion independent of the presence of additional stimuli required instead for sLPS. The ability of rLPS of activating the inflammasome in vitro has as a direct consequence a higher efficiency of rLPS-exposed DCs in activating natural killer (NK) cells compared to sLPS-exposed DCs. However, diversely from possible predictions, we found that the different efficiencies of the two LPS species in eliciting innate responses are almost nullified in vivo. Therefore, sLPS and rLPS induce nearly similar in vivo innate responses but with different mechanisms of signaling. © 2011 Elsevier B.V.
Articolo in rivista - Articolo scientifico
DCs; Inflammasome; Innate immunity; Lipopolysaccharide; NFAT; NK cells; Animals; Dendritic Cells; Immunity, Innate; Inflammasomes; Killer Cells, Natural; Lipopolysaccharides; Mice; Mice, Inbred C57BL; O Antigens; Signal Transduction; Immunology; Immunology and Allergy
English
2012
142
1-2
41
47
none
Zanoni, I., Bodio, C., Broggi, A., Ostuni, R., Caccia, M., Collini, M., et al. (2012). Similarities and differences of innate immune responses elicited by smooth and rough LPS. IMMUNOLOGY LETTERS, 142(1-2), 41-47 [10.1016/j.imlet.2011.12.002].
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/68565
Citazioni
  • Scopus 37
  • ???jsp.display-item.citation.isi??? 35
Social impact