Immune Response

Invasion of macrophages activates the host im­mune system to begin a series of attacks against MAP-infected macrophages. This further leads to activation of T cells, including CD4+ T helper cells and cytolytic CD8+ cells (Radostits et al., 2007).

Numerous γδ T cells have been detected in early lesions (Kruger et al., 2015a), but these cells were low in numbers at later stages (Valheim et al., 2004; Lybeck et al., 2013). This could imply an important role for γδ T cells in the early immune response.

A CD4+ T-helper type-1 response with IFN-γ production is regarded as essential since it further activates macrophages (Stabel, 2006). This cellular immune response has generally been associated with controlled infection in most animals. In line with this, granulomatous lesions with few bacteria showed large num­bers of CD4+ T cells (Kruger et al., 2015a). In goats exposed to MAP under natural condi­tions, IFN-γ responses were detected earlier in non-shedders than in shedders, but the strong­est responses were later found in goats shedding MAP (Mercier et al., 2016; Souriau et al., 2017). This suggests that an early IFN-γ response is im­portant for controlling the infection. The IFN-γ response may wane with progressive infection (Singh et al., 2013), but this cellular response may also persist during later stages (Lybeck et al., 2011; Kohler et al., 2015). Animals that are unable to control the disease will usually de­velop a humoral immune response along with increased shedding of bacteria in faeces, eventu­ally followed by the onset of clinical symptoms (Olsen et al., 2002).

Several infectious foci in the intestine will develop, and there will be an ongoing battle between the host and the bacteria in these vari­ous foci. The local immune responses in the foci may differ, and both humoral and cellular im­mune responses can sometimes be present at the same time.

The timing of both pro- and anti­inflammatory responses are likely to be criti­cal for the outcome of infection. Studies in calves and sheep have suggested that the anti­inflammatory cytokine IL-10 might reduce severity of disease and increase protective im­munity (Subharat et al., 2012; de Silva et al., 2013), but high IL-10 has also been associated with progressive or severe MAP infection in goats (Lybeck et al., 2013; Singh et al., 2013). Recently, RNA sequencing of MAP antigen stimulated peripheral blood mononuclear cells (PBMC) has been performed. Among the find­ings were repression of proinflammatory re­sponses by downregulation of IFN-γ and IL-17 related responses, in addition to upregulation of IL-18 binding protein in infected compared with non-infected animals 1 month post-infection (Berry et al., 2018). Such new tools could help increase our knowledge on protective immune responses to MAP.

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