# Effect of periostin (OSF-2) on phagocytosis of Plasmodium-infected erythrocytes

## TL;DR

Periostin (OSF-2) can both increase and decrease the phagocytosis of malaria-infected red blood cells, depending on the presence of uninfected cells.

## Contribution

Discovery of OSF-2's dual role in modulating phagocytosis of Plasmodium-infected erythrocytes.

## Key findings

- OSF-2 increases phagocytosis of purified Plasmodium-infected erythrocytes.
- OSF-2 reduces phagocytosis when rosetting is induced by uninfected erythrocytes.
- The effect of OSF-2 on phagocytosis is CD36-dependent and reversible.

## Abstract

Phagocytosis is a pivotal component of the human innate immune defense against malaria. This essential defense mechanism is often modulated by various host-derived soluble factors. We investigated the phagocytosis of Plasmodium falciparum- and P. knowlesi-infected erythrocytes (IRBC) by human monocytic THP-1 cells in the presence of periostin (OSF-2), a human secretory protein involved in inflammation and tissue repair. This focus was prompted by the fact that OSF-2 is a potent stimulator of Plasmodium IRBC rosette formation, a parasite-derived cytoadherence phenomenon known to impede phagocytosis.

Culturable parasite isolates were recruited, and tested with the THP-1 cells and recombinant human OSF-2 protein. The role of OSF-2 in IRBC phagocytosis by the phagocytes was evaluated in the presence and absence of uninfected erythrocytes (URBC), and the receptor involved was investigated with antibody blocking assay.

OSF-2 exerted a dual role. When rosetting was prevented via IRBC purification, OSF-2 increased IRBC phagocytosis. This stimulatory effect was also seen when THP-1 cells were primed with OSF-2 before IRBC exposure. This OSF-2-mediated phagocytosis was CD36-dependent and rapidly reversible upon OSF-2 removal. However, when rosetting was induced by the addition of URBC, the presence of OSF-2 reduced the rate of IRBC phagocytosis.

These findings highlight the complex parasite-host interactions influencing the infection pathogenesis.