The latest Paper of the Month for Parasitology is “Immunological mechanisms involved in macrophage activation and polarization in schistosomiasis” and is freely available.

Schistosomiasis, caused by Schistosoma sp. parasite is a neglected infectious disease that affects over 200 million people worldwide, particularly those living in low-income areas with poor sanitary services. The parasite’s life cycle includes the infected snails that release cercariae (larvae) into freshwater, which penetrate human skin. The larvae mature into adult worms in the human body, releasing eggs into the bloodstream to continue the life cycle. Symptoms of schistosomiasis range from mild to severe, including itchy skin, fever, cough, diarrhea, and hepatosplenomegaly. The formation of inflammatory lesions and granulomas around trapped parasite eggs determines the severity because they can cause tissue fibrosis. The only drug available for schistosomiasis is Praziquantel, which cannot revert fibrosis and possesses low efficacy against some strains of Schistosoma. Therefore, there is an urgent need to develop new therapeutic strategies, to overcome the effects of this disease.

Our recent publication entitled “Immunological mechanisms involved in macrophage activation and polarization in schistosomiasis,” provided new insights into the role of macrophages in S. mansoni and S. japonicum infection and perspectives to use these cells as a target for new approaches using immunotherapy. Macrophages play a critical role in the body’s response to infection. These cells can acquire different phenotypes depending on the type of stimulus they receive. M1 macrophages are called ‘classically activated’ and exhibit a pro-inflammatory phenotype, while M2 macrophages or ‘alternatively activated’ are considered anti-inflammatory cells.

The polarization of macrophages into these two subtypes can dictate the severity of schistosomiasis; however, we still do not fully understand how these cells are activated during different stages of schistosomiasis. This knowledge gap may interfere with the development of immunotherapies for schistosomiasis. To address this issue, we conducted in vitro and in vivo studies that investigated the participation of macrophages in schistosomiasis.

Our results demonstrated that activation and polarization of M1 and M2 macrophages depend on antigenic stimulus derived from different evolutive forms of S. mansoni and S. japonicum. Specifically, we observed that antigens derived from cercariae, schistosomula, and adult worms induced the M1 profile. In contrast, egg antigens predominantly induce the M2 profile. On the other hand, data related to adult worms remains controversial and indicates that antigens derived from this form can induce both M1 and M2 profiles. Thus, our findings suggest that the polarization of M1 and M2 macrophages depends on the stage of infection since M1 macrophages are more predominant in the early stages and M2 macrophages are more abundant in the later stages.

The mechanisms involved in macrophage M1/M2 polarization during schistosomiasis is relevant and complex. The role of S. japonicum and S. mansoni antigens in this process is crucial, as they have immunomodulatory effects in different phases of the disease and may be a therapeutic target, especially in the chronic phase. In addition, the combination of different schistosome antigens can enhance host protection due to the stimulation of an adequate immune response, including activation of either an M1 or M2 profile. These findings provide a promising clue for further research on using macrophages in immunotherapy for schistosomiasis.

The paper “Immunological mechanisms involved in macrophage activation and polarization in schistosomiasis” by Irlla Correia Lima Licá, Gleycka Cristine Carvalho Gomes Frazão, Ranielly Araujo Nogueira, Maria Gabriela Sampaio Lira, Vitor Augusto Ferreira dos Santos, João Gustavo Mendes Rodrigues, Guilherme Silva Miranda, Rafael Cardoso Carvalho, Lucilene Amorim Silva, Rosane Nassar Meireles Guerra, Flávia Raquel Fernandes Nascimento, published in Parasitology, is freely available.