Mycobacterium tuberculosis19-kDa Lipoprotein Promotes Neutrophil Activation

Abstract

Certain microbial substances, e.g., LPS, can activate neutrophils or prime them to enhance their response to other activating agents, e.g., fMLP. We investigated the role of the Mycobacterium tuberculosis (MTB) 19-kDa lipoprotein in activation of human neutrophils. MTB 19-kDa lipoprotein initiated phenotypic changes characteristic of neutrophil activation, including down-regulation of CD62 ligand (L-selectin) and up-regulation of CD35 (CR1) and CD11b/CD18 (CR3, Mac-1). In addition, exposure of neutrophils to MTB 19-kDa lipoprotein enhanced the subsequent oxidative burst in response to fMLP as assessed by oxidation of dihydrorhodamine 123 (determined by flow cytometry). LPS also produced these effects with similar kinetics, but an oligodeoxynucleotide containing a CpG motif failed to induce any priming or activation response. Although the effects of LPS required the presence of serum, neutrophil activation by MTB 19-kDa lipoprotein occurred independently of serum factors, suggesting the involvement of different receptors and signaling mechanisms for LPS and MTB 19-kDa lipoprotein. Thus, MTB 19-kDa lipoprotein serves as a pathogen-associated molecular pattern that promotes neutrophil priming and activation.

Triggering Receptor Expressed on Myeloid Cells-1 in Neutrophil Inflammatory Responses: Differential Regulation of Activation and Survival

“…In inflammation, neutrophil activation occurs i.e., in the presence of IL-8, IFN-␥, and heat shock proteins (3,5,6), or is initiated upon recognition of Ab or complement opsonized particles (4). In addition, PMN directly recognize microbial products via pathogen recognition receptors or Toll-like receptors (TLR) (7)(8)(9)(10).…”

A mutant of Mycobacterium tuberculosis lacking the 19-kDa lipoprotein Rv3763 is highly attenuated in vivo but retains potent vaccinogenic properties

“…In addition, exposure of neutrophils to MTB 19-kDa lipoprotein enhanced a subsequent oxidative burst [15]. Exposure of macrophages to this protein may also induce cell death, allowing escape and dissemination [16].…”

“…It was interesting to note that the inflammatory response in the lungs to the Δ19 was minimal, and in fact there is evidence that the 19kDa-lipoprotein is a major mediator of neutrophil activation, including down-regulation of CD62L (L-selectin) and up-regulation of CD35 (CR1) and CD11b/CD18 (CR3, Mac-1) [15]. In addition, exposure of neutrophils to MTB 19-kDa lipoprotein enhanced a subsequent oxidative burst [15].…”

“…Given that the Δ19 mutant grew perfectly well in culture media (data not shown), this seems to suggest that the 19kDa-lipoprotein plays an important role in the host cell phagosome, enabling pathogen cell division. This mutant thus falls into the category of live attenuated vaccines, several of which have been evaluated in animal models [14].It was interesting to note that the inflammatory response in the lungs to the Δ19 was minimal, and in fact there is evidence that the 19kDa-lipoprotein is a major mediator of neutrophil activation, including down-regulation of CD62L (L-selectin) and up-regulation of CD35 (CR1) and CD11b/CD18 (CR3, Mac-1) [15]. In addition, exposure of neutrophils to MTB 19-kDa lipoprotein enhanced a subsequent oxidative burst [15].…”

Broadening Our View About the Role of Mycobacterium tuberculosis Cell Envelope Components During Infection: A Battle for Survival

“…Neutrophils can kill M.tb through both oxidative and non-oxidative processes (Brown et al, 1987;Jones et al, 1990). Although neutrophils may interact with M.tb cell wall components during alveolar deposition [such as the 19-KDa lipoglycoprotein, SL-1 and PGLs (Faldt et al, 1999;Neufert et al, 2001;L. Zhang et al, 1991)], there is no information regarding how alveolar neutrophil-derived hydrolases affect the integrity of the cell wall of M.tb during infection.…”