Abstract
One complication of malaria is increased susceptibility to invasive bacterial infections. Plasmodium infections impair host immunity to non-Typhoid Salmonella (NTS) through heme-oxygenase I (HO-I)-induced release of immature granulocytes and myeloid cell-derived IL-10. Yet, it is not known if these mechanisms are specific to NTS. We show here, that Plasmodium yoelii 17XNL (Py) infected mice had impaired clearance of systemic Listeria monocytogenes (Lm) during both acute parasitemia and up to 2 months after clearance of Py infected red blood cells that was independent of HO-I and IL-10. Py-infected mice were also susceptible to Streptococcus pneumoniae (Sp) bacteremia, a common malaria-bacteria co-infection, with higher blood and spleen bacterial burdens and decreased survival compared to naïve mice. Mechanistically, impaired immunity to Sp was independent of HO-I, but was dependent on Py-induced IL-10. Splenic phagocytes from Py infected mice exhibit an impaired ability to restrict growth of intracellular Lm, and neutrophils from Py-infected mice produce less reactive oxygen species (ROS) in response to Lm or Sp. Analysis also identified a defect in a serum component in Py-infected mice that contributes to reduced production of ROS in response to Sp. Finally, treating naïve mice with Plasmodium-derived hemozoin containing naturally bound bioactive molecules, excluding DNA, impaired clearance of Lm. Collectively, we have demonstrated that Plasmodium infection impairs host immunity to diverse bacteria, including S. pneumoniae, through multiple effects on innate immunity, and that a parasite-specific factor (Hz+bound bioactive molecules) directly contributes to Plasmodium-induced suppression of antibacterial innate immunity.
Highlights
Despite efforts to decrease the global health burden of malaria, infections with Plasmodium species continue to cause over 200 million episodes of malaria each year (Organization WH, 2018)
To examine how Plasmodium may suppress innate immunity during systemic bacterial infection, C57BL/6N mice were first infected with Plasmodium yoelii 17XNL (Py) that resulted in increasing parasitemia through about 3-weeks post infection that was followed by resolution of detectable infected red blood cells (RBCs) during the ensuing week (Figure 1A)
Identifying specific cell functions and broad, systemic deficiencies in innate immune responses during Plasmodium infections that are responsible for diminished bacterial immunity is necessary to improve the treatment of these cases
Summary
Despite efforts to decrease the global health burden of malaria, infections with Plasmodium species continue to cause over 200 million episodes of malaria each year (Organization WH, 2018). In areas with endemic malaria, an association between Plasmodium infection and invasive bacterial infections has been reported, and malaria was identified as a major risk factor for developing bacteremia that correlated with a worse clinical outcome and higher morbidity (Berkley et al, 2005; Reddy et al, 2010; Colombatti et al, 2011; Scott et al, 2011; Were et al, 2011; Auma et al, 2013; Gomez-Perez et al, 2014; Morton et al, 2018). Plasmodium-induced hemolysis results in the activation of heme oxygense-1 (HO-1), which mobilizes functionally immature granulocytes from the bone marrow These immature granulocytes exhibited impaired production of reactive oxygen species in response to PMA stimulation, and decreased killing of NTS (Cunnington et al, 2011). These represent important knowledge gaps that impede treatment of bacteria co-infections during malaria
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
