Likewise, although it is clear that neutrophil phagocytosis of parasite antigen, merozoites, iRBC and possibly gametocytes occurs (35, 36, 40, 121), it is unknown whether antibodies promoting neutrophil phagocytosis are protective

Likewise, although it is clear that neutrophil phagocytosis of parasite antigen, merozoites, iRBC and possibly gametocytes occurs (35, 36, 40, 121), it is unknown whether antibodies promoting neutrophil phagocytosis are protective. young children and pregnant women are especially susceptible to disease. Malaria is a large public health burden with an estimated 216 million cases of malaria being reported in 2016, resulting in an estimated 445,000 deaths (6). Globally most disease caused by infection with is caused by (6). Pathology is thought to be due to a combination of the sequestration of infected red blood cells (iRBC) in the microvasculature, endothelial activation, as well as pro-coagulant and importantly pro-inflammatory responses (7). In this review, we assess the literature examining how neutrophils and parasites interact, and the mechanisms by which neutrophils can play an active role in parasite clearance. Neutrophil Dynamics and 17-DMAG HCl (Alvespimycin) Recruitment to Sites of Parasite Sequestration Changes in peripheral blood neutrophil levels have been described during infections. In controlled human malaria infections (CHMI) in non-immune individuals, neutrophil numbers are stable during the asymptomatic liver stage (8). In naturally-infected individuals, patterns of change in peripheral blood neutrophil numbers vary with the cohort studied. Using hematological data from over 3,000 children, Olliaro et al. estimated that peripheral blood neutrophil counts increase about 43% (95% CI 26C35%) during acute uncomplicated malaria, and that the level of increase is positively associated with parasitaemia (9). In semi-immune travelers neutrophil counts were higher in those with severe malaria compared to those with uncomplicated malaria, while in non-immune travelers, though neutrophil counts increased with the presence of infection, neutrophil counts did not vary with disease severity (10). A study in HIV-infected individuals showed no difference in neutrophil numbers when comparing those with and without asymptomatic infection (11), whereas pregnant women with infection had lower numbers of peripheral blood neutrophils than uninfected women (12). Differences between cohorts are likely due to disease status classification (clinical malaria or asymptomatic parasitemia), immune status and/or age. Neutrophils are a heterogenous population and this is important because different neutrophil subsets can have varying functional properties, for example CD177+ neutrophils are also positive for Proteinase 3, and IL17+ neutrophils have increased ROS production [reviewed in (13)]. We know that neutrophils from individuals infected with behave differently compared to those from non-infected individuals (14C18), and a subset of neutrophils with impaired oxidative burst have been observed in individuals infected with (18), suggesting that neutrophil subsets change during the course of infection. In individuals challenged with LPS, inflammation results in the release of a neutrophil subset that suppresses T cell activation (19), whether this occurs during infection is unclear but it is one example of why work to identify neutrophil subsets in infections would likely yield valuable information into the role of Rabbit Polyclonal to Cyclin H neutrophils in malaria. Neutrophils are generally the first circulating cells to respond to an invading pathogen. However, how and 17-DMAG HCl (Alvespimycin) whether neutrophils are recruited to the sites of iRBC sequestration is still unclear. We know very little regarding neutrophil expression of receptors involved in migration and adhesion. There is no evidence that neutrophil adhesion molecule CD11a changes with infection (18), and expression by neutrophils of other adhesion molecules such as CD18, CD11b, and CD62L is still unstudied. There is more information on the expression of neutrophil receptors on endothelial cells. Expression of receptors on endothelial cells involved in neutrophil adhesion and migration are likely increased with infection. Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and the endothelial leukocyte adhesion molecule E-selectin are increased on endothelial cells after exposure to iRBC [reviewed in (20)] and this is supported 17-DMAG HCl (Alvespimycin) by observations showing increased levels of soluble E-selectin and soluble ICAM-1 in the blood of infected individuals (21). Regarding chemokines involved in neutrophil recruitment, neutrophil chemoattractant protein CXCL8 is increased in peripheral blood of patients with severe malaria [reviewed in (22)] (23) as well as in the cerebral spinal fluid (CSF) of children with cerebral malaria and in the placentas of women with malaria in pregnancy [reviewed in (22)]. In addition, antigen can induce the production of neutrophil recruitment chemokines CXCL1 and Interleukin 8 17-DMAG HCl (Alvespimycin) (IL8) production by endothelial cells and the production of Interleukin 8 17-DMAG HCl (Alvespimycin) (IL8) by placental syncytiotrophoblast [reviewed in (22)]. Interestingly, although increased expression of neutrophil chemoattractants occurs, studies of malaria pathology rarely show significant neutrophil infiltration at sites of sequestration. Low numbers of neutrophils were reported in the brain microvasculature in autopsy samples from children in Malawi (14), and neutrophil numbers were.