In recent years, the role of IL-9 has gained attention in several immunological contexts; however, it has not been possible to classify this cytokine as part of a particular specific response, since it has been reported to be produced during type 1, 2, and 3 immune responses [1]. Throughout the years, IL-9 has been characterized as a pleiotropic cytokine capable of modifying the function of several cells [2], highlighting its role on the promotion of activation, expansion and degranulation of mast cells (MC), induction of proliferation in innate lymphoid cells (ILCs) and upregulation of dendritic cells (DC) functions, in allergic, autoimmune, cancer and infectious contexts [1], [3], [4], [5], [6], [7], [8], [9], [10]. Additionally, the potential cellular targets for IL-9 have expanded, and it is now clear that this cytokine is able to regulate a wide variety of cells depending on the inflammatory milieu [1].

The cellular sources of IL-9 are diverse: from innate cells like MC, Natural Killer T cells (NKT), and ILCs, to the immune adaptative compartment, including CD4+ and CD8+ T cells, although most of the work has focused within the CD4+ T helper subset [2], [3]. TH2 were the first subset of CD4+ cells linked to the production of this cytokine [11]; however, in 2008 TH9 cells were discovered as a specific cell lineage that preferentially produce this cytokine in response to IL-4 and TGF-β [12], [13]. Furthermore, in recent years it has been reported that the signaling pathways of IL-25, IL-1β, TSLP, IL-33 and amphiregulin are capable of potentiating the differentiation of TH9 cells, which, together with TGF-β and IL-4 signals, polarize differentiation through the transcription factors SMAD2/3/4, PU.1, IRF4, STAT6, STAT5, GATA3, and HIF1⍺ [14], [15]. In this sense, TH9 lymphocytes have been studied as new players in adaptative responses as one the main producers of IL-9, involved in allergy, autoimmunity, cancer, viral and parasitic infections [9], [10], [16], [17], [18], [19], [20]. Additionally, other CD4+ subsets have been linked to the production of IL-9, such as TH17 and Treg [21], [22], [23], [24]; however, the biological function of this expression is still unclear, and IL-9 secretion by Treg is still debatable.

TH9 cells have risen as critical mediators of the type 2 immune responses against parasites [25], defined as an organism that lives at the expense of the host [25]. Parasites are classified according to their location in relation to the host: endoparasites, which live inside the host, and ectoparasites, which live on the external surface of the host. Endoparasites include protozoa and helminths, and helminths are further divided into cestodes (flatworms), nematodes (roundworms), and trematodes (flukes). Among endoparasites, tapeworms and hookworms are the most representative. Ectoparasites are typically arthropod like lice, fleas, ticks and mites [25].

In this review, we aimed to summarize the latest findings regarding the roles of TH9 cells during the settings of parasitic infections, seeking to provide a comprehensive overview of the up-to-date knowledge, highlighting both the opportunities for therapeutic intervention and the challenges that remain in understanding the complexity of TH9-IL-9 mediated responses during parasitic infections.