Why does Hyper IgM syndrome predispose to P jirovecii infections?

Here is an interesting concept.

We know that in Hyper IgM syndrome, there is an inability to undergo normal class-switching or somatic hypermutation in B cells.

It is characterized by normal level of B cells with diminished levels of IgG, IgE and IgA and with high levels of IgM.

That is why, these patients are susceptible to infections by extracellular pathogens that require class-switched antibodies for clearance, such as pyogenic bacteria.

But why would it predispose to P jirovecii (P. carni) infections? Pneumocystis doesn't require antibodies for clearance!

Here's why: The interaction between T cells and dendritic cells via CD40L-CD40 is essential for upregulating co-stimulatory molecules on dendritic cells. Dendritic cells activate T cells, which in turn, activate macrophages. Intracellular pathogens, such as mycobacteria are P jirovecii are normally killed by activated macrophages which is why patients with CD40L deficiency are prone to these infections.

That's all!
-IkaN

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