Eosinophils: Allergies and Parasites, Day 21

Eosinophils are granulocytic cells 𝘥𝘦𝘧𝘦𝘯𝘥𝘪𝘯𝘨 𝘢𝘨𝘢𝘪𝘯𝘴𝘵 𝘩𝘦𝘭𝘮𝘪𝘯𝘵𝘩𝘪𝘤 𝘱𝘢𝘳𝘢𝘴𝘪𝘵𝘦𝘴 𝘢𝘯𝘥 𝘤𝘰𝘯𝘵𝘳𝘪𝘣𝘶𝘵𝘪𝘯𝘨 𝘵𝘰 𝘢𝘭𝘭𝘦𝘳𝘨𝘪𝘤 𝘪𝘯𝘧𝘭𝘢𝘮𝘮𝘢𝘵𝘪𝘰𝘯. Their 𝘤𝘺𝘵𝘰𝘵𝘰𝘹𝘪𝘤 𝘱𝘳𝘰𝘵𝘦𝘪𝘯𝘴, and 𝘳𝘦𝘴𝘱𝘰𝘯𝘴𝘦 𝘵𝘰 𝘢𝘯𝘥 𝘮𝘰𝘥𝘶𝘭𝘢𝘵𝘪𝘯𝘨 𝘩𝘪𝘴𝘵𝘢𝘮𝘪𝘯𝘦, affects local inflammation and systemic immune responses [1,2]. 

𝗠𝗲𝗰𝗵𝗮𝗻𝗶𝘀𝘁𝗶𝗰 𝗢𝘃𝗲𝗿𝘃𝗶𝗲𝘄: 𝗛𝗶𝘀𝘁𝗮𝗺𝗶𝗻𝗲 𝗮𝗻𝗱 𝗘𝗼𝘀𝗶𝗻𝗼𝗽𝗵𝗶𝗹 𝗔𝗰𝘁𝗶𝘃𝗮𝘁𝗶𝗼𝗻 
𝗛𝗶𝘀𝘁𝗮𝗺𝗶𝗻𝗲 𝗥𝗲𝗰𝗲𝗽𝘁𝗼𝗿𝘀 𝗼𝗻 𝗘𝗼𝘀𝗶𝗻𝗼𝗽𝗵𝗶𝗹𝘀 
Human eosinophils express 𝘏2𝘙 𝘢𝘯𝘥 𝘏4𝘙. Activation of these receptors induces responses including 𝘤𝘢𝘭𝘤𝘪𝘶𝘮 𝘪𝘯𝘧𝘭𝘶𝘹, shape change, changes in adhesion molecules, and upregulation of activation markers like CD69 [3]. 

𝗠𝗼𝗱𝘂𝗹𝗮𝘁𝗶𝗼𝗻 𝗼𝗳 𝗚𝗲𝗻𝗲 𝗘𝘅𝗽𝗿𝗲𝘀𝘀𝗶𝗼𝗻 𝗮𝗻𝗱 𝗥𝗲𝗰𝗲𝗽𝘁𝗼𝗿 𝗨𝗽𝗿𝗲𝗴𝘂𝗹𝗮𝘁𝗶𝗼𝗻 
In 𝘢𝘵𝘰𝘱𝘪𝘤 𝘥𝘦𝘳𝘮𝘢𝘵𝘪𝘵𝘪𝘴, histamine stimulation via H₄R upregulates IL-18Rα on eosinophils, making them more responsive to IL-18 [3]. 

𝗔𝗺𝗽𝗹𝗶𝗳𝗶𝗰𝗮𝘁𝗶𝗼𝗻 𝗯𝘆 𝗖𝘆𝘁𝗼𝗸𝗶𝗻𝗲 𝗠𝗶𝗹𝗶𝗲𝘂 
Histamine acts in concert with 𝘛𝘩2 𝘤𝘺𝘵𝘰𝘬𝘪𝘯𝘦𝘴 (𝘐𝘓-5, 𝘐𝘓-13) 𝘢𝘯𝘥 𝘐𝘍𝘕-γ 𝘵𝘰 𝘱𝘰𝘵𝘦𝘯𝘵𝘪𝘢𝘵𝘦 𝘦𝘰𝘴𝘪𝘯𝘰𝘱𝘩𝘪𝘭 𝘢𝘤𝘵𝘪𝘷𝘢𝘵𝘪𝘰𝘯. For example, preincubation with histamine plus IFN-γ increases ECP (eosinophil cationic protein) expression upon IL-18 challenge [3]. 

𝘐𝘯 𝘝𝘪𝘷𝘰 𝗘𝘃𝗶𝗱𝗲𝗻𝗰𝗲 𝘃𝗶𝗮 𝗛𝟰𝗥 ‘
Animal models show that eosinophils 𝘥𝘦𝘧𝘪𝘤𝘪𝘦𝘯𝘵 𝘪𝘯 𝘏4𝘙 𝘩𝘢𝘷𝘦 𝘳𝘦𝘥𝘶𝘤𝘦𝘥 𝘢𝘤𝘵𝘪𝘷𝘢𝘵𝘪𝘰𝘯 𝘪𝘯 𝘤𝘦𝘳𝘵𝘢𝘪𝘯 𝘪𝘯𝘧𝘭𝘢𝘮𝘮𝘢𝘵𝘪𝘰𝘯 𝘴𝘦𝘵𝘵𝘪𝘯𝘨𝘴, demonstrating partial activation mediated by histamine signaling 𝘪𝘯 𝘷𝘪𝘷𝘰 [4]. 

𝗚𝗲𝗿𝗺𝗮𝗻 𝗥𝗲𝘀𝗲𝗮𝗿𝗰𝗵𝗲𝗿𝘀 
Holger Stark (Heinrich Heine University, Düsseldorf) co-authored work shows that eosinophils from atopic dermatitis patients express high levels of H₄R and that histamine via H₂R / H₄R strongly regulates the IL-18/IL-18R axis and activation markers such as CD69 [3]. 

𝗦𝗽𝗲𝗰𝘂𝗹𝗮𝘁𝗶𝘃𝗲 𝗛𝘆𝗽𝗼𝘁𝗵𝗲𝘀𝗶𝘀 ´𝘏𝘪𝘴𝘵𝘢𝘮𝘪𝘯𝘦 𝘗𝘳𝘪𝘮𝘪𝘯𝘨 𝘚𝘸𝘪𝘵𝘤𝘩 (𝘏𝘗𝘚)´: 
In allergic or parasitic contexts, low-level histamine primed state in eosinophils via H₄R and H₂R, upregulating IL-18Rα. Upon 𝘴𝘦𝘤𝘰𝘯𝘥𝘢𝘳𝘺 𝘴𝘵𝘪𝘮𝘶𝘭𝘪 (𝘩𝘪𝘨𝘩 𝘢𝘯𝘵𝘪𝘨𝘦𝘯 𝘭𝘰𝘢𝘥), the primed eosinophils act quickly, degranulating, and amplifying inflammation.  This switch mechanism allows eosinophils to act as both sensors and effectors. 

Stay tuned for 𝗗𝗮𝘆 𝟮𝟮: 𝗕𝗮𝘀𝗼𝗽𝗵𝗶𝗹𝘀 𝗮𝗻𝗱 𝗠𝗮𝘀𝘁 𝗖𝗲𝗹𝗹𝘀 – 𝗔𝗹𝗹𝗲𝗿𝗴𝘆 𝗠𝗲𝗱𝗶𝗮𝘁𝗼𝗿𝘀 

𝗥𝗲𝗳𝗲𝗿𝗲𝗻𝗰𝗲𝘀 
1. doi: 10.3389/falgy.2025.1585142 
2. DOI: 10.1007/0-387-33778-4_12 
3. DOI: 10.3390/ijms231810294 
4. DOI: 10.3389/fimmu.2018.02119   

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