Expression of Cathelicidin LL-37 duringMycobacterium tuberculosisInfection in Human Alveolar Macrophages, Monocytes, Neutrophils, and Epithelial Cells

Abstract

The innate immune response in human tuberculosis is not completely understood. To improve our knowledge regarding the role of cathelicidin hCAP-18/LL37 in the innate immune response to tuberculosis infection, we used immunohistochemistry, immunoelectron microscopy, and gene expression to study the induction and production of the antimicrobial peptide in A549 epithelial cells, alveolar macrophages (AM), neutrophils, and monocyte-derived macrophages (MDM) after infection with Mycobacterium tuberculosis. We demonstrated that mycobacterial infection induced the expression and production of LL-37 in all cells studied, with AM being the most efficient. We did not detect peptide expression in tuberculous granulomas, suggesting that LL-37 participates only during early infection. Through the study of Toll-like receptors (TLR) in MDM, we showed that LL-37 can be induced by stimulation through TLR-2, TLR-4, and TLR-9. This last TLR was strongly stimulated by M. tuberculosis DNA. We concluded that LL-37 may have an important role in the innate immune response against M. tuberculosis.

Leukotriene B4 Modulates P2X7 Receptor–MediatedLeishmania amazonensisElimination in Murine Macrophages

“…In particular, LL-37 has been shown to kill Leishmania infections both in vitro (46,47) and in vivo (48). Additionally, LTB4 induces the release of LL-37 in some cell types (49). Thus, it tempting to hypothesize that LL-37 may be acting in L. amazonensis-infected macrophages by favoring the innate immunity through paracrine activation of the P2X7 receptor.…”

The innate immune response in human tuberculosis

“…Crucially, AECs control the composition of ASL. ASL contains anti‐microbial peptides that have been implicated in Mtb resistance, such as β‐defensin 2 (Rivas‐Santiago et al ., 2005), cathelicidin (LL‐37) (Rivas‐Santiago et al ., 2008) and hepcidin (Sow et al ., 2011), as well as a variety of cytokines and chemokines that are secreted by AECs to recruit and activate phagocytes (reviewed in Li et al ., 2012). …”

Neutrophil-derived azurocidin alarms the immune system

“…LL-37, for example, is stored in secondary granules of PMN and therefore, discharged rapidly upon extravasation of PMN [8]. In addition, LL-37 is induced in monocytes or macrophages by proinflammatory stimuli [9] and secreted into the surrounding. Alarmins exert chemotactic and activating effects on APC.…”