Expression of Chemokines and Induction of Rapid Cell Death in Human Blood Neutrophils by Mycobacterium tuberculosis

Abstract

To elucidate the role of neutrophils in the early inflammatory response to mycobacterial infection, expression of chemokines interleukin (IL)-8 and macrophage inflammatory protein-1alpha (MIP-1alpha) was examined in human blood neutrophils in response to the lipopolysaccharide (LPS) of Escherichia coli, which induces acute inflammation, or to Mycobacterium tuberculosis or purified protein derivative (PPD), which induce chronic mycobacterial inflammation. Neutrophils stimulated with LPS, M. tuberculosis, or PPD expressed both IL-8 and MIP-1alpha. Expression of IL-8 and MIP-1alpha was lower after stimulation with M. tuberculosis or PPD than after stimulation with LPS, but the kinetics of expression did not differ significantly. In contrast, both M. tuberculosis and PPD with tumor necrosis factor-alpha induced neutrophils to undergo rapid cell death, which might remove neutrophils and activate macrophages at sites of mycobacterial inflammation. The findings suggest that neutrophils play important roles in the host defense against mycobacterial infection.

Induction of apoptosis in human neutrophils by Mycobacterium tuberculosis is dependent on mature bacterial lipoproteins

“…Unopsonized and opsonized Mtb induced apoptosis to a level of 26 and 35% respectively compared to spontaneously apoptotic control cells (8%) (Fig. 3B), confirming previous findings [7,11,17]. Human PMNs infected with virulent Mtb displayed an Mtb or from Mtb-induced apoptotic PMNs.…”

“…The fact that Mtb-induced apoptosis of PMNs triggers chemokine expression [7] and heat shock protein release [11], and the finding that the number of apoptotic cells (26%) exceeded the number of phagocytosing cells (<5%), suggest that soluble factors are involved in the induction of apoptosis. However, we were unable to detect any direct effects of soluble factors from either Mtb or Mtb-induced apoptotic PMNs.…”

“…PMNs that infiltrate the tissue infected with Mtb participate not only in removal of the bacteria [6], but also in the orchestration of inflammation through release of cytokines and chemokines [7]. PMNs have a short lifespan of 24-72 hours and apoptotic cells are usually cleared by macrophages, mediating an anti-inflammatory response [8].…”

“…PMNs have a short lifespan of 24-72 hours and apoptotic cells are usually cleared by macrophages, mediating an anti-inflammatory response [8]. Components of the Mtb cell wall or whole bacteria activate PMNs and induce apoptosis [7,9,10] but in contrast to spontaneously apoptotic PMNs, clearance of Mtb-induced apoptotic PMNs by macrophages is accompanied by a pro-inflammatory activation [11]. Hence, apoptotic PMNs are important cells in the initial innate immune reaction to Mtb infection and it is therefore vital to understand how Mtb induce apoptosis in inflammatory cells.…”

Early granuloma formation after aerosol Mycobacterium tuberculosis infection is regulated by neutrophils via CXCR3‐signaling chemokines

“…Expression of several chemokines is up-regulated upon M. tuberculosis infection, but a correlation with anti-tuberculous protection has been difficult to establish [14][15][16][17][18][19][20][21]. Thus far, a significant loss of resistance was only observed in CCR2 -/-mice [22,23].…”