Visceral leishmaniasis patients display altered composition and maturity of neutrophils as well as impaired neutrophil effector functions

Immunologically, active visceral leishmaniasis (VL) is characterised by profound immunosuppression, severe systemic inflammatory responses and an impaired capacity to control parasite replication. Neutrophils are highly versatile cells, which play a crucial role in the induction as well as the resolution of inflammation, the control of pathogen replication and the regulation of immune responses. Neutrophil functions have been investigated in human cutaneous leishmaniasis, however, their role in human visceral leishmaniasis is poorly understood. In the present study we evaluated the activation status and effector functions of neutrophils in patients with active VL and after successful anti-leishmanial treatment. Our results show that neutrophils are highly activated and have degranulated; high levels of arginase, myeloperoxidase and elastase, all contained in neutrophils’ granules, were found in the plasma of VL patients. In addition, we show that a large proportion of these cells are immature. We also analysed effector functions of neutrophils that are essential for pathogen clearance and show that neutrophils have an impaired capacity to release neutrophil extracellular traps, produce reactive oxygen species and phagocytose bacterial particles, but not Leishmania parasites. Our results suggest that impaired effector functions, increased activation and immaturity of neutrophils play a key role in the pathogenesis of VL

First record of Aleuroclava psidii (Singh) and Aleurotrachelus tuberculatus Singh (Hemiptera: Aleyrodidae) in East Africa

Two Asian whiteflies, Aleurotrachelus tuberculatus Singh 1933 and Aleuroclava psidii (Singh 1931), are recorded for the first time in Africa. Both species were found on Psidium guajava L. (Myrtaceae) in the Coast and Dar es Salaam regions of Tanzania. It is not possible to determine when these species might have been introduced, due to the absence of a routine monitoring system for pest introductions in East African countries. However, no records exist of their presence or damage caused to plants in Africa, therefore they have been likely introduced recently. In addition, Aleurodicus dispersus Russell, a widespread, polyphagous whitefly species, was also collected on guava. This species was introduced to Tanzania in 2003 from a putative Asian origin. This fact, coupled with the new introductions reported here, suggests that a pathway exists for the importation of exotic insects or noxious pest species from Asia to East Africa

Malnutrition in Healthy Individuals Results in Increased Mixed Cytokine Profiles, Altered Neutrophil Subsets and Function.

Malnutrition is commonly associated with increased infectious disease susceptibility and severity. Whereas malnutrition might enhance the incidence of disease as well as its severity, active infection can in turn exacerbate malnutrition. Therefore, in a malnourished individual suffering from a severe infection, it is not possible to determine the contribution of the pre-existing malnutrition and/or the infection itself to increased disease severity. In the current study we focussed on two groups of malnourished, but otherwise healthy individuals: moderately malnourished (BMI: 18.4-16.5) and severely malnourished (BMI <16.5) and compared several immune parameters with those of individuals with a normal BMI (≥18.5). Our results show a similar haematological profile in all three groups, as well as a similar ratio of CD4+ and CD8+ T cells. We found significant correlations between low BMI and increased levels of T helper (Th) 1 (Interferon (IFN)-γ, (interleukin (IL)-2, IL-12), Th2 (IL-4, IL-5, IL-13), as well as IL-10, IL-33 and tumor necrosis factor-α, but not IL-8 or C reactive protein. The activities of arginase, an enzyme associated with immunosuppression, were similar in plasma, peripheral blood mononuclear cells (PBMC) and neutrophils from all groups and no differences in the expression levels of CD3ζ, a marker of T cell activation, were observed in CD4+ and CD8+T cells. Furthermore, whereas the capacity of neutrophils from the malnourished groups to phagocytose particles was not impaired, their capacity to produce reactive oxygen species was impaired. Finally we evaluated the frequency of a subpopulation of low-density neutrophils and show that they are significantly increased in the malnourished individuals. These differences were more pronounced in the severely malnourished group. In summary, our results show that even in the absence of apparent infections, healthy malnourished individuals display dysfunctional immune responses that might contribute to increased susceptibility and severity to infectious diseases

Disease severity in patients with visceral leishmaniasis is not altered by co-infection with intestinal parasites

Visceral leishmaniasis (VL) is a neglected tropical disease that affects the poorest communities and can cause substantial morbidity and mortality. Visceral leishmaniasis is characterized by the presence of Leishmania parasites in the spleen, liver and bone marrow, hepatosplenomegaly, pancytopenia, prolonged fever, systemic inflammation and low body mass index (BMI). The factors impacting on the severity of VL are poorly characterized. Here we performed a cross-sectional study to assess whether co-infection of VL patients with intestinal parasites influences disease severity, assessed with clinical and haematological data, inflammation, cytokine profiles and BMI. Data from VL patients was similar to VL patients co-infected with intestinal parasites, suggesting that co-infection of VL patients with intestinal parasites does not alter disease severity

Arginase activity in plasma, PBMCs and neutrophils of individuals with normal and low BMI.

<p>Arginase activity in plasma, PBMCs and neutrophils of individuals with normal and low BMI.</p

Frequency of LDGs in PBMCs.

<p>PBMCs from individuals with normal BMI (n = 17) and low BMI (n = 23, of which 9 were moderately malnourished and 14 were severely malnourished) were isolated by density gradient centrifugation and the frequency of LDGs (CD15+arginase+ cells) was determined by flow cytometry. Fig 5A shows the correlation between BMI and the frequency of LDGs and statistical significance was established using a Spearman rank test. Fig 5B shows the frequency of LDGs between the individuals with a normal BMI, moderately malnourished and severely malnourished individuals and statistical significance was established using a Kruskal-Wallis test.</p

Levels of Th2 cytokines in plasma.

<p>The plasma from individuals with normal BMI (n = 17) and low BMI (n = 23, of which 9 were moderately malnourished and 14 were severely malnourished) was tested by Luminex for the levels of IL-4, IL-5 and IL-13. Fig 2A, C and E show correlations between BMI and the different cytokines and statistical significance was established using a Spearman rank test. Fig B, D and F show cytokine levels between the individuals with a normal BMI, moderately malnourished and severely malnourished individuals and statistical significance was established using a Kruskal-Wallis test.</p