**7.2 Cytokines**

Strongyloidiasis promotes the robust Th2-type immune response with the production of cytokines, such as IL-3, IL-4, IL-5, IL-6, IL-9, IL-10 and IL-13. Contrarily, Th1-type responses are reduced during nematode infection (Wilkes et al., 2007; Patel et al., 2009).

IL-3 is important during *Strongyloides* infection stimulates the synthesis of potent mast cells and basophils enhancing the function of these cells (Abe et al., 1993*).* In addition, IL-3 can enhance the levels of intra-cellular IL-4 upon activating basophils, with anti-IgE and IL-3 contributing to an increase in eosinophils (Kimura et al., 2006; Lantz et al., 2008).

In addition, this association reduces the efficacy of anthelmintic drugs, increasing the prevalence of infection (Montes et al., 2009; Iriemenam et al., 2010). Stool examinations should be performed with special attention to detect *S. stercoralis* larvae in all patients

The relationship between *S. stercoralis* and its host is complex, and little is known about the immunomodulatory mechanisms that regulate this interaction. Different factors are involved, including the capacity of the parasite to replicate, the adequacy of the host immune response, and the ability of the parasite to evade those responses (Grove, 1994;

During helminthic infection, Th2-type cell-dependent host defences that involve CD4 cells are developed (Maizels & Yazdanbakhsh, 2003; Anthony et al., 2007). In human hosts and animal models, the cellular immune response to *Strongyloides* infection is characterised by intraepithelial and tissue eosinophils, neutrophils and mast cells with Th2-type production of cytokines such as IL-4, IL-5 and IL-13. Conversely, Th1-type responses are downregulated during nematode infection (El-Malky et al., 2003; Paterson et al., 2008; Iriemenam

Eosinophils are essential against nonphagocytosable parasites, such as *Strongyloides,* that cannot be ingested because of their large size. Eosinophils defend the host by attacking the parasite via the FcεRI receptor, capturing antigens from the worms and presenting the antigens to T cells to initiate an antigen-specific immune response (Galioto et al., 2006; Padigel et al., 2006; Iriemenam et al., 2010). Others mechanisms may be involved, including antibody-dependent cellular cytotoxicity (ADCC) mediated by eosinophils on the parasite surface, which releases toxic molecules in an attempt to eliminate the parasite (Ligas et al.,

Mast cells have an important role in the defence against *S. stercoralis* by inhibiting the invasion of the adult worm into the intestinal epithelium, promoting the stimulation of gut motility, mucus release and expulsion of the parasites. In addition, mast cells induce the

Strongyloidiasis promotes the robust Th2-type immune response with the production of cytokines, such as IL-3, IL-4, IL-5, IL-6, IL-9, IL-10 and IL-13. Contrarily, Th1-type responses

IL-3 is important during *Strongyloides* infection stimulates the synthesis of potent mast cells and basophils enhancing the function of these cells (Abe et al., 1993*).* In addition, IL-3 can enhance the levels of intra-cellular IL-4 upon activating basophils, with anti-IgE and IL-3

attraction and modulation of eosinophils (Kobayashi et al., 1998; Concha et al., 2005).

are reduced during nematode infection (Wilkes et al., 2007; Patel et al., 2009).

contributing to an increase in eosinophils (Kimura et al., 2006; Lantz et al., 2008).

infected by HTLV-1 (Carvalho & Da Fonseca Porto, 2004).

**7. Host-parasite interaction** 

**7.1 Cellular immune response** 

Trajman et al., 1997).

et al., 2010).

**7.1.1 Eosinophils** 

**7.1.2 Mast cells** 

**7.2 Cytokines** 

2003; Klion & Nutman, 2004).

IL-4 has multiple immunoregulatory functions, including T-cell growth factor activity, B-cell regulation, serum IgE level enhancement, and stimulation of the growth and/or differentiation of macrophages, hematopoietic cells, and mast cells (Urban et al., 1991; Negrão-Correa et al., 2006; Wilkes et al., 2007). IL-4 decreases the fecundity and survival of adult worms and increases intestinal smooth muscle contraction, facilitating the expulsion of the parasite (Concha et al., 2005).

IL-5 regulates the production of eosinophil myelocyte precursors in bone marrow, the development of mature eosinophils after helminth infection and, in most instances, the production of a number of other cytokines, including IL-4 and IL-13, and chemokines such as RANTES and eotaxin (Herbert et al., 2000; Klion & Nutman, 2004; Mir et al., 2006).

IL-13 also participates in the defence mechanisms against helminths, promoting an increase in the intestinal fluid content and increased smooth muscle contractility, a phenomenon that may contribute to worm expulsion (Porto et al., 2001; Shea-Donohue & Urban, 2004; Patel et al., 2009).

#### **7.3 Humoral immune response**

The humoral immune response complements defence mechanisms against strongyloidiasis with the production of immunoglobulins by plasma cells. Several immunoglobulins, such as IgE, IgG and IgM, are essential for the elimination of the parasite (Ligas et al., 2003; Machado et al., 2005).

IgE antibodies can mediate the activation of accessory cells and the recognition of parasite antigens, promoting goblet cell mucus secretion and the degranulation of mast cells that release mediators affecting parasite survival (Machado et al., 2009). IgG and IgM can transfer immunity against the human parasite in the presence of the complement system and neutrophils (Abraham et al., 1995; Vadlamudi et al., 2006)

Laboratory models have suggested that both T and B cells mediate the immune response through an increase in immunoglobulins, eosinophils and mast cells and hyperplasia of goblet cells, which require interleukins and chemokines for their development and activation. In strongyloidiasis, dexamethasone seems to primarily suppress cytokines such as IL-1β, IL-4, VEGF, TNF-α, IFN-γ, IL-3, IL-4, IL-5, IL-10 and IL-12 and decreases the production of IgG and IgE antibodies during *S. venezuelensis* infection (Machado et al., 2011; Tefé-Silva et al., 2012).
