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Updated: May 10, 2026
An In vitro Co-infection Model to Study Plasmodium falciparum-HIV-1 Interactions in Human Primary Monocyte-derived Immune Cells
Published on: August 15, 2012
Influenza-induced alveolar macrophages protect against death by malaria-associated acute lung injury
Abstract:
Lower respiratory tract infections are common in malaria-endemic areas, and there is some evidence that co-infections between various bacteria/viruses and Plasmodium may affect disease prognosis. In this study, we report the novel finding that co-infection with influenza/A/X31 protects mice from death by Plasmodium berghei NK65-Edinburgh, a model of severe malarial pulmonary leak which underpins malaria-associated acute lung injury (MA-ALI) and malaria-associated acute respiratory distress (MA-ARDS). Co-infected mice exhibit equivalent parasitemia as mice with malaria only, suggesting that the survival phenotype is due to differences in immune kinetics. We demonstrated that the pulmonary leak typical of Pb E is attenuated in co-infected mice without alteration in CD8 T cell activation and recruitment to the lung. Upon further examination of the immune response to influenza/A/X31 we identified a population of arginase 1-expressing alveolar macrophages that traffic to the lungs early during infection. In vitro these macrophages inhibit CD8 T cell activation and proliferation better than non-arginase expressing cells. Removal of arginase-1 expressing alveolar macrophages in vivo via administration of the antimetabolite gemcitabine removed the protective effects of influenza/A/X31co-infection on MA-ALI. This study opens a route to better understanding of how to modulate the immunopathology observed in pulmonary leak associated with severe malaria, which must be achieved to rationally design therapeutic interventions for MA-ARDS / MA-ALI.
Insights
Influenza co-infection protects mice from severe malaria-associated lung injury by altering immune cell responses. Arginase 1-expressing macrophages are key to this protective effect, offering new therapeutic targets for acute respiratory distress.
Area of Science:
- Immunology
- Infectious Diseases
- Pulmonology
Background:
- Lower respiratory tract infections are common in malaria-endemic regions.
- Co-infections with Plasmodium parasites and other pathogens may impact disease severity.
- Malaria-associated acute lung injury (MA-ALI) and acute respiratory distress (MA-ARDS) are severe complications.
Purpose of the Study:
- To investigate the effect of influenza A virus co-infection on malaria-induced lung injury in a mouse model.
- To identify the immune mechanisms underlying the observed protective effect of co-infection.
Main Methods:
- A mouse model of severe malaria (Plasmodium berghei NK65-Edinburgh) co-infected with influenza A/X31.
- Assessment of parasitemia, pulmonary leak, and CD8 T cell responses.
- Identification and functional characterization of alveolar macrophages.
- In vivo depletion of arginase-1 expressing macrophages using gemcitabine.
Main Results:
- Influenza/A/X31 co-infection protected mice against lethal Plasmodium berghei NK65-Edinburgh infection and attenuated pulmonary leak.
- Pulmonary leak reduction occurred without altering CD8 T cell activation or recruitment.
- Arginase 1-expressing alveolar macrophages were identified in the lungs during co-infection.
- These macrophages inhibited CD8 T cell activation in vitro.
- Depletion of these macrophages reversed the protective effect of co-infection on MA-ALI.
Conclusions:
- Influenza co-infection confers protection against severe malaria-induced lung injury.
- Arginase 1-expressing alveolar macrophages play a critical role in mediating this protection.
- Targeting these macrophages could offer novel therapeutic strategies for MA-ALI and MA-ARDS.
