B Cells Produce the Tissue-Protective Protein RELMα during Helminth Infection, which Inhibits IL-17 Expression and Limits Emphysema.

Emphysema results in destruction of alveolar walls and enlargement of lung airspaces and has been shown to develop during helminth infections through IL-4R-independent mechanisms. We examined whether interleukin 17A (IL-17A) may instead modulate development of emphysematous pathology in mice infected with the helminth parasite Nippostrongylus brasiliensis. We found that transient elevations in IL-17A shortly after helminth infection triggered subsequent emphysema that destroyed alveolar structures. Furthermore, lung B cells, activated through IL-4R signaling, inhibited early onset of emphysematous pathology. IL-10 and other regulatory cytokines typically associated with B regulatory cell function did not play a major role in this response. Instead, at early stages of the response, B cells produced high levels of the tissue-protective protein, Resistin-like molecule α (RELMα), which then downregulated IL-17A expression. These studies show that transient elevations in IL-17A trigger emphysema and reveal a helminth-induced immune regulatory mechanism that controls IL-17A and the severity of emphysema.

Stridor and emphysema due to cystic echinococcosis in cattle and buffalo intermediate hosts in Punjab, India.

The clinical symptoms associated with hydatid disease in the bovine populations remain largely unknown and the disease is usually considered asymptomatic in these intermediate hosts. We report occurrence of symptoms such as sudden onset of continuous stridor, coughing and wheezing due to hydatid cysts present in the lungs of infected cattle and buffalo. Two cattle and one buffalo presented to the Teaching Veterinary Hospital, Guru Angad Dev Veterinary & Animal Sciences University with the complaint of continuous stridor, coughing and wheezing with normal feed and water intake were followed up. The comprehensive clinical examination followed by haematology, radiography of upper and lower respiratory tract, ultrasonography of lungs, liver and reticulum revealed presence of multiple hydatid cysts in the lung parenchyma. There was presence of subcutaneous emphysema in one of the infected animal. Radiography revealed cysts occupying up to 60% of alveolar space in the lungs. Endoscopy up to hilus was carried out to rule out the presence of any other mass/lesion in the respiratory tract. Per cutaneous aspiration (Ultrasound guided) of cystic fluid confirmed the diagnosis and fertile nature of hydatid cysts. The current study reports association of stridor and emphysema with hydatid disease in bovine hosts and it is important that veterinary practitioners in endemic areas consider hydatid disease for differential diagnosis when investigating the etiology of stridor and emphysema in bovine intermediate hosts.

TGF-ß-responsive myeloid cells suppress type 2 immunity and emphysematous pathology after hookworm infection.

Transforming growth factor ß (TGF-ß) regulates inflammation, immunosuppression, and wound-healing cascades, but it remains unclear whether any of these functions involve regulation of myeloid cell function. The present study demonstrates that selective deletion of TGF-ßRII expression in myeloid phagocytes i) impairs macrophage-mediated suppressor activity, ii) increases baseline mRNA expression of proinflammatory chemokines/cytokines in the lung, and iii) enhances type 2 immunity against the hookworm parasite Nippostrongylus brasiliensis. Strikingly, TGF-ß-responsive myeloid cells promote repair of hookworm-damaged lung tissue, because LysM(Cre)TGF-ßRII(flox/flox) mice develop emphysema more rapidly than wild-type littermate controls. Emphysematous pathology in LysM(Cre)TGF-ßRII(flox/flox) mice is characterized by excessive matrix metalloprotease (MMP) activity, reduced lung elasticity, increased total lung capacity, and dysregulated respiration. Thus, TGF-ß effects on myeloid cells suppress helminth immunity as a consequence of restoring lung function after infection.